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Original Paper

Open Access Gateway

Telocytes in Pregnancy-Induced Physiological Liver Growth

Wang F.a · Bei Y.b, c · Zhao Y.a · Song Y.a · Xiao J.b, d · Yang C.a

Author affiliations

aDivision of Gastroenterology and Hepatology, Digestive Disease Institute, Tongji Hospital, Tongji University School of Medicine, Shanghai, bRegeneration and Ageing Lab, Experimental Center of Life Sciences, School of Life Science, Shanghai University, Shanghai, cSchool of Communication and Information Engineering, Shanghai University, Shanghai, dShanghai Key Laboratory of Bio-Energy Crops, School of Life Science, Shanghai University, Shanghai, China

Corresponding Author

Professor Changqing Yang and Dr. Junjie Xiao

Division of Gastroenterology and Hepatology, Digestive Disease Institute, Tongji

Hospital, Tongji University School of Medicine, 389 Xin Cun Road, Shanghai 200065

(China); and Regeneration and Ageing Lab, Experimental Center of Life Sciences, School

of Life Science, Shanghai University, 333 Nan Chen Road, Shanghai 200444 (China)

E-Mail changqingyang_tj@hotmail.com and E-Mail junjiexiao@live.cn

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Cell Physiol Biochem 2015;36:250-258

Abstract

Background/Aims: We previously documented the presence of Telocytes (TCs) in liver and further indicated the potential roles of TCs in liver regeneration after hepatectomy. Pregnancy-induced liver growth, other than liver regeneration after hepatectomy, is a physiological hepatic adaption to meet the enhanced nutritional and metabolic demands. However, the possible roles of TCs in pregnancy-induced liver growth remain unknown. Methods: Pregnant mice were sacrificed at different time points (pregnancy day 0.5, 4.5, 8.5, 10.5, 12.5, 14.5, 16.5, and 18.5). The liver weight was used to evaluate the liver growth during pregnancy. Hepatocytes proliferation was determined by albumin and 5-ethynyl-2'- deoxyuridine (EdU) double immunostaining while TCs were counted by double immunolabeling for CD34/PDGFR-α. Results: Pregnancy-induced liver growth was preceded by increased proliferation of hepatocytes at pregnancy day 4.5, 8.5, 14.5 and 16.5. Furthermore, the number of TCs in liver detected by double immunolabeling for CD34/PDGFR-α was significantly increased at pregnancy day 4.5 and day 14.5, that was coincident with the occurrence of two peaks of hepatic cell proliferation during pregnancy. Conclusion: Our results suggest a possible relationship between TCs and hepatocyte proliferation in pregnancy-induced liver growth.

© 2015 S. Karger AG, Basel


Keywords

Telocytes · Liver growth · Pregnancy · Hepatocytes · Liver regeneration ·


Introduction

Liver has an extraordinary ability to regenerate after injury and surgical resection, principally mediated by the proliferation of remaining hepatocytes and the differentiation of liver stem cells [1,2,3]. However, liver regenerative capacity can be grievously altered upon severe and chronic liver injury [4,5,6], and is negatively affected by aging [7,8,9]. Other than liver regeneration after injury and resection, pregnancy-induced liver growth is a physiological hepatic adaption to meet the enhanced nutritional and metabolic demands for developing placenta and fetus [10,11,12,13]. It has previously been shown that pregnancy is able to increase liver regenerative capacity in aged liver, suggesting its potential therapeutic value in liver failure [14]. However, the mechanisms underlying maternal hepatic adaptions to pregnancy are poorly elucidated.

Telocytes (TCs), a novel type of interstitial cell population firstly identified by Popescu's group, are characterized by a small cell body and extremely long prolongations named telopodes (Tps) with alternating thin segments (podomers) and dilated segments (podoms) [15] (see http://www.telocytes.com). FIB-SEM tomography, the most advanced and powerful technique to visualize cells confirmed the existence of TCs [16]. Since their identification in 2010, TCs have been found in various mammalian organs and tissues and contribute to form a complex interstitial network for the maintenance of tissue homeostasis, such as heart [17,18,19,20,21], lung [22,23,24], placenta [25], pancreas [26,27], skin [28,29], skeletal muscle [30,31,32], uterus [33,34,35,36,37,38], urinary system [39,40,41], and others [42,43,44,45,46,47,48,49,50,51,52,53,54,55]. Furthermore, increasing evidence has demonstrated the presence of TCs within stem cell niches [23,29,31,49,56,57] and indicated the potential involvement of TCs in tissue regeneration/repair after injury [32,38,58,59,60,61,62,63,64]. Our group has recently identified the presence of TCs in liver [54], and further demonstrated a close relationship between TCs and the cells (hepatocytes/stem cells) essentially involved in liver regeneration using a murine model of partial hepatectomy [65]. The aim of the present study was to likewise investigate the possible roles of TCs in hepatic adaptions to pregnancy.

Materials and Methods

Animals

Eight-week-old female C57BL/6 mice, purchased from Shanghai SLAC Laboratory Animal Center, were maintained in a temperature-controlled room on a 12 h light/dark cycle, with ad libitum access to food and water. Mice were mated and the presence of a copulatory plug in the vagina was considered as gestation day 0.5. Pregnant mice were then designed to be sacrificed at different time points (pregnancy day 0.5, 4.5, 8.5, 10.5, 12.5, 14.5, 16.5, and 18.5) (n=8 per group). The liver weight was measured to evaluate liver growth during pregnancy. Frozen liver sections were used for immunofluroscent staining. This study was approved by the local ethical committees and all animal experiments were conducted under the guidelines on the use and care of laboratory animals for biomedical research published by National Institutes of Health (No. 85-23, revised 1996).

EdU and Albumin double labelled staining

Mice were intraperitoneally injetected with 50 mg/kg of 5-ethynyl-2'-deoxyuridine (EdU) 1 h before sacrificed. The frozen sections (6 um) were fixed with 4% paraformaldehyde for 30 min after washed with PBS, and then incubated with Albumin primary antibody (1:100, BS6520, Bioworld) in diluted by PBS containing 0.25% Triton X-100 overnight at 4°C. After that, sections were incubated with anti-rabbit Rhodamine-conjugated secondary antibody (1:200, Sc-362262, Santa Cruz) for 1 h at room temperature. After wash with PBS, staining with anti-EdU working solution was performed at room temperature for 30 min according to the manual of a EdU detection kit (Click-iT Plus EdU Alexa Fluor 647 Imaging Kit, Life Technology). Finnally, sections were stained with DAPI (Prolong® Gold, Life Technology) and observed under a confocal laser scanning microscope (LSM 710, Carl Zeiss MicroImaging GmbH). The results were expressed as EdU and Albumin double positive cell number per mm2.

Immunofluorescent staining for CD34/PDGFR-α

Double immunolabeling for CD34/PDGFR-α, considered as the specific markers for TCs, was used for detection of TCs in the present study 66. Briefly, 6 μm-thick frozen liver sections were fixed in 4% paraformaldehyde for 15 min, washed with PBS for three times, pre-incubated in PBS supplemented with 10% goat serum for 1 h, and then incubated overnight at 4°C with rabbit polyclonal anti-PDGFR-α (Abcam, ab61219) and rat monoclonal anti-CD34 (Abcam, ab8158) primary antibodies diluted by 1:100 in PBS with 0.25% Triton X-100. After that, sections were exposed for 1 h to goat anti-rat labeled with FITC (Santa Cruz, sc-2011) and goat anti-rabbit labeled with rhodamine (Santa Cruz, sc-362262) secondary antibodies diluted by 1:200 in the same buffer. Finally, sections were stained with DAPI (ProLong® Gold, Life technology). The images were analyzed with confocal laser scanning microscope (LSM 710, Carl Zeiss MicroImaging GmbH, Germany) under an amplification of 400×.

EdU and CD34 double labelled staining

EdU and CD34 double labelled staining was used to determine the proliferative TCs. In brief, 6 μm-thick frozen liver sections were fixed in 4% paraformaldehyde for 15 min, washed with PBS for three times, pre-incubated in PBS supplemented with 10% goat serum for 1 h, and then incubated overnight at 4°C with rat monoclonal anti-CD34 (Abcam, ab8158) primary antibodies diluted by 1:100 in PBS with 0.25% Triton X-100. After that, sections were exposed for 1 h to goat anti-rat labeled with FITC (Santa Cruz, sc-2011) secondary antibodies diluted by 1:200 in the same buffer. After wash with PBS, staining with anti-EdU working solution was performed at room temperature for 30 min according to the manual of a EdU detection kit (Click-iT Plus EdU Alexa Fluor 647 Imaging Kit, Life Technology). Finally, sections were stained with DAPI (ProLong® Gold, Life technology). The images were analyzed with confocal laser scanning microscope (LSM 710, Carl Zeiss MicroImaging GmbH, Germany) under an amplification of 400×.

Statistical analysis

Data are expressed as mean ± SEM. All analyses were performed using SPSS 19.0. Statistical significance was determined with one-way ANOVA test followed by two-tailed Student's t test. Significance is defined as P-value less than 0.05.

Results

Liver weight continued to increase which appeared significant from pregnancy day 10.5 as compared to day 0.5 in pregnant mice (Fig. 1), indicating that pregnancy induces liver growth.

Fig. 1

Liver growth during pregnancy. Liver weight during pregnancy. *, p<0.05 vs. pregnancy day 0.5.

http://www.karger.com/WebMaterial/ShowPic/135946

EdU and Albumin double immunostaining was conducted to investigate the proliferative effect of pregnancy-induced liver growth. As compared to pregnancy day 0.5, EdU positive hepatocytes number per mm2 of liver tissues was significantly increased in early stage (day 4.5 and 8.5) and late stage (day 14.5 and 16.5) of pregnancy (Fig. 2).

Fig. 2

Pregnancy-induced liver growth preceded via increased hepatocytes proliferation. Quantitative analysis of Albumin and 5-ethynyl-2'- deoxyuridine (EdU) double positive cells in liver tissues (left panel) showed significant increase of EdU positive hepatocytes number per mm2 in early stage (day 4.5 and 8.5) and late stage (day 14.5 and 16.5) of pregnancy. Representative images of Albumin (red) and EdU (yellow) double positive cells, counterstained with DAPI (blue) for nuclei at pregnancy day 0.5 and 14.5 were shown in the right panel. Original magnification 400 ×; Scale bar = 20 μm. *,P<0.05 vs. pregnancy day 0.5.

http://www.karger.com/WebMaterial/ShowPic/135945

As labeled by double immunofluorescent staining for CD34 and PDGFR-α, the number of CD34/PDGFR-α positive cells (TCs) per mm2 of liver tissues was significantly increased at pregnancy day 4.5 and 14.5 (Fig. 3A and B), which was in accordance with the time points when high level of hepatocytes proliferation rate occurred during pregnancy. However, as indicated by immunofluorescent staining for CD34 and EdU (Fig. 4), we did not observe significant difference among the time points we have checked, which might be due to the fact that the rate of proliferative TCs was extremely low or proliferative endothelial cells might cover up the true changes of proliferative TCs.

Fig. 3

Detection for TCs in liver by double immunolabeling for CD34/PDGFR-α. A Representative images of CD34/PDGFR-α double immunolabeling in pregnant liver. CD34 (green) and PDGFR-α (red) double positive cells were pointed with arrows. Nuclei were counterstained with DAPI (blue). Original magnification 400 ×; Scale bar = 20 μm. B Quantitative analysis of CD34/PDGFR-α positive cell number per mm2 in pregnant liver. *, p<0.05 vs. pregnancy day 0.5.

http://www.karger.com/WebMaterial/ShowPic/135944

Fig. 4

Detection for proliferative TCs in liver by immunolabeling for CD34/EdU. A Representative images of CD34/EdU immunolabeling in pregnant liver. Original magnification 400 ×; Scale bar = 20 μm. B Quantitative analysis of CD34/EdU positive cell number per mm2 in pregnant liver.

http://www.karger.com/WebMaterial/ShowPic/135943

Discussion

The present study shows that pregnancy-induced liver growth preceded via increased proliferation of hepatocytes. Furthermore, the number of TCs in liver detected by double immunolabeling for CD34/PDGFR-α was significantly increased at pregnancy day 4.5 and day 14.5, that was coincident with the occurrence of two peaks of hepatocytes proliferation during pregnancy. These results suggest the potential involvements of TCs in hepatic proliferative adaptions to pregnancy.

To date, the mechanisms underlying hepatic adaptions to pregnancy are largely unknown [10,11,13,14,67,68,69]. In the present study, we demonstrated two peaks of hepatocytes proliferation occurring at early stages and late stages of pregnancy as shown by EdU and Albumin double immunostaining. The increased proliferation of hepatocytes related to pregnancy has previously been documented [13,14,67,69], while the occurrence of two proliferative peaks of hepatocytes during pregnancy in the present study was firstly reported here. We hypothesized that the possible reasons may be related to different species (rat vs. mouse) [13], ages (old vs. young) [14], and animal models (pregnancy vs. ovariectomy or pseudopregnancy) [14,67] applied in our study and in others. In addition, the metabolic and hormonal mechanisms underlying hepatocyte proliferation during pregnancy need to be further explored.

Previously, our group documented the presence of TCs in liver and further indicated the potential roles of TCs in liver regeneration after hepatectomy, probably by influencing hepatocyte proliferation and/or liver stem cell differentiation [65]. In the present study, we further demonstrated the increased number of CD34/PDGFR-α positive TCs in pregnant liver at the same time points (pregnancy day 4.5 and day 14.5) when the two proliferative peaks of hepatocytes appeared, suggesting a possible relationship between TCs and hepatocytes proliferation in pregnancy-induced liver growth. Increasing evidence has shown that TCs are critically implicated in tissue regeneration/repair by forming a complicated network with tissue/organ-specific cells, immunoreactive cells, other interstitial cells and stem cells, and thus actively contribute to intercellular signaling coordination either by minute intercellular junctions or by paracrine effect via ectovesicles [23,29,30,56,57,59,70]. However, the exact mechanisms how TCs might affect the proliferative capacity of hepatocytes in pregnancy-induced liver growth remain to be further studied.

A major limitation of the present study is that the data presented here does not fully demonstrated a functional relation between TCs and hepatocyte proliferation in pregnancy-induced liver growth. We have also conducted CD34 plus EdU immunostaining, however, no significant difference was observed among the time points we had checked. We speculated that this was due to the fact that the rate of proliferative TCs was extremely low because pregnancy-induced physiological liver growth was a weak physiological stimuli. Besides that, as CD34 is also a marker for endothelial cells, thus proliferative endothelial cells might cover up the true changes of proliferative TCs. It would be interesting to check the rate of proliferative TCs using CD34/PDGFR-α/EdU three immunostainings in other liver regeneration models such as partial hepatectomy (PH) models. Nevertheless, considering the fact that pregnancy-induced liver growth preceded via increased proliferation of hepatocytes at pregnancy day 4.5, 8.5, 14.5 and 16.5 while the number of TCs in liver was significantly increased at pregnancy day 4.5 and day 14.5, we think that TCs proliferate first (or at least at the same time) compared with hepatocytes and therefore a possible relationship between TCs and hepatocyte proliferation in pregnancy-induced liver growth might exist.

In conclusion, the present study demonstrates an increase of CD34/PDGFR-α positive TCs in pregnant liver accompanied by high level of hepatocyte proliferation. Considering that liver regeneration capacity is usually far from ideal in certain circumstances like severe liver injury or surgical resection, understanding how TCs take effect in pregnancy-induced physiological liver growth might raise bright prospect for the treatment of liver failure.

Disclosure Statement

The authors declare there are no conflicts of interest.

Acknowledgments

This work was supported by the grants from National Natural Science Foundation of China (81070343 and 81370559 to C. Yang; 81200169 to J. Xiao; 81400635 to F. Wang; 81400647 to Y. Bei), funds from Shanghai Innovation Program (12431901002 to C. Yang), Innovation Program of Shanghai Municipal Education Commission (13YZ014 to J. Xiao), Foundation for University Young Teachers by Shanghai Municipal Education Commission (year 2012, to J. Xiao), Innovation fund from Shanghai University (sdcx2012038 to J. Xiao), and Program for the integration of production, teaching and research for University Teachers supported by Shanghai Municipal Education Commission (year 2014, to J. Xiao), Jonit Projects in Major Diseases funding from Shanghai Municipal Commission of Health and Family Planning (2014ZYJB0201 to C. Yang), Jonit Projects for Novel Frontier Technology in Shanghai Municipal Hospital from Shanghai Municipal Commission of Health and Family Planning (SHDC1204122 to C. Yang), Shanghai Medical Guide Project from Shanghai Science and Technology Committee (14411971500 to F. Wang), grants from Chinese Foundation for Hepatitis Prevention and Control (TQGB20140141 to F. Wang) and funds from Shanghai Innovation Program (12431901002 to C. Yang), and China Postdoctoral Science Foundation (2014M561456 to Y. Bei).


References

  1. Kandilis AN, Koskinas J, Tiniakos DG, Nikiteas N, Perrea DN: Liver regeneration: focus on cell types and topographic differences. Eur Surg Res 2010:44:1-12.
  2. Itoh T, Miyajima A: Liver regeneration by stem/progenitor cells. Hepatol Baltim Md 2014:59:1617-1626.
  3. Duncan AW, Soto-Gutierrez A: Liver repopulation and regeneration: new approaches to old questions. Curr Opin Organ Transplant 2013:18:197-202.
  4. Little SA, Jarnagin WR, DeMatteo RP, Blumgart LH, Fong Y: Diabetes is associated with increased perioperative mortality but equivalent long-term outcome after hepatic resection for colorectal cancer. J Gastrointest Surg 2002:6:88-94.
  5. Wang DW, Yin YM, Yao YM: Advances in the management of acute liver failure. World J Gastroenterol 2013:19:7069-7077.
  6. Serenari M, Cescon M, Cucchetti A, Pinna AD: Liver function impairment in liver transplantation and after extended hepatectomy. World J Gastroenterol 2013:19:7922-7929.
  7. Bucher NL, Swaffield MN, Ditroia JF: The influence of upon the incorporation of thymidine-2C14 into the DNA of regenerating rat liver. Cancer Res 1964:24:509-512.
  8. Iakova P, Awad SS, Timchenko NA: Aging reduces proliferative capacities of liver by switching pathways of C/EBPalpha growth arrest. Cell 2003:113:495-506.
  9. Timchenko LT, Salisbury E, Wang GL, Nguyen H, Albrecht JH, Hershey JW, Timchenko NA: Age-specific CUGBP1-eIF2 complex increases translation of CCAAT/enhancer-binding protein beta in old liver. J Biol Chem 2006:281:32806-32819.
  10. Mesbah MM, Baldwin RL: Effects of diet, pregnancy, and lactation on enzyme activities and gluconeogenesis in ruminant liver. J Dairy Sci 1983:66:783-788.
  11. Hollister A, Okubara P, Watson JG, Chaykin S: Reproduction in mice: liver enlargement in mice during pregnancy and lactation. Life Sci 1987:40:11-18.
  12. Dickmann LJ, Tay S, Senn TD, Zhang H, Visone A, Unadkat JD, Hebert MF, Isoherranen N: Changes in maternal liver Cyp2c and Cyp2d expression and activity during rat pregnancy. Biochem Pharmacol 2008:75:1677-1687.
  13. Bustamante JJ, Copple BL, Soares MJ, Dai G: Gene profiling of maternal hepatic adaptations to pregnancy. Liver Int 2010:30:406-415.
  14. Gielchinsky Y, Laufer N, Weitman E, Abramovitch R, Grabot Z, Bergman Y, Pikarsky E: Pregnancy restores the regenerative capacity of the aged liver via activation of an mTORC1-controlled hyperplasia/hypertrophy switch. Genes Dev 2010:24:543-548.
  15. Popescu LM, Faussone-Pellegrini MS: TELOCYTES - a case of serendipity: the winding way from Interstitial Cells of Cajal (ICC), via Interstitial Cajal-Like Cells (ICLC) to TELOCYTES. J Cell Mol Med 2010:14:729-740.
  16. Cretoiu D, Hummel E, Zimmermann H, Gherghiceanu M, Popescu LM: Human cardiac telocytes: 3D imaging by FIB-SEM tomography. J Cell Mol Med 2014:18:2157-2164.
  17. Kostin S: Myocardial telocytes: a specific new cellular entity. J Cell Mol Med 2010:14:1917-1921.
  18. Faussone-Pellegrini MS, Bani D: Relationships between telocytes and cardiomyocytes during pre- and post-natal life. J Cell Mol Med 2010:14:1061-1063.
  19. Popescu LM, Manole CG, Geherghiceanu M, Ardelean A, Nicolescu MI, Hinescu ME, Kostin S. Telocytes in human epicardium. J Cell Mol Med 2010:14:2085-2093.
  20. Gherghiceanu M, Manole CG, Popescu LM: Telocytes in endocardium: electron microscope evidence. J Cell Mol Med 2010:14:2330-2334.
  21. Yang Y, Sun W, Wu SM, Xiao J, Kong X: Telocytes in human heart valves. J Cell Mol Med 2014:18:759-765.
  22. Zheng Y, Li H, Manole CG, Sun A, Ge J, Wang X: Telocytes in trachea and lungs. J Cell Mol Med 2011:15:2262-2268.
  23. Popescu LM, Gherghiceanu M, Suciu LC, Manole CG, Hinescu ME: Telocytes and putative stem cells in the lungs: electron microscopy, electron tomography and laser scanning microscopy. Cell Tissue Res 2011:345:391-403.
  24. Rusu MC, Jianu AM, Mirancea N, Didilescu AC, Manoiu VS, Paduraru D: Tracheal telocytes. J Cell Mol Med 2012:16:401-405.
  25. Suciu L, Popescu LM, Gherghiceanu M, Regalia T, Nicolescu MI, Hinescu ME, Faussone-Pellegrini MS: Telocytes in human term placenta: morphology and phenotype. Cells Tissues Organs 2010:192:325-339.
  26. Nicolescu MI, Popescu LM: Telocytes in the interstitium of human exocrine pancreas: ultrastructural evidence. Pancreas 2012:41:949-956.
  27. Bosco C, Díaz E, Gutiérrez R, González J, Pérez J: Ganglionar nervous cells and telocytes in the pancreas of Octodon degus: extra and intrapancreatic ganglionar cells and telocytes in the degus. Auton Neurosci Basic Clin 2013:177:224-230.
  28. Rusu MC, Mirancea N, Manoiu VS, Valcu M, Nicolescu MI, Paduraru D: Skin telocytes. Ann Anat 2012:194:359-367.
  29. Ceafalan L, Gherghiceanu M, Popescu L M, Simionescu O: Telocytes in human skin-are they involved in skin regeneration? J Cell Mol Med 2012:16:1405-1420.
  30. Popescu LM, Manole E, Serboiu CS, Manole CG, Suciu LC, Gherghiceanu M, Popescu BO: Identification of telocytes in skeletal muscle interstitium: implication for muscle regeneration. J Cell Mol Med 2011:15:1379-1392.
  31. Bojin FM, Gavriliuc OI, Cristea MI, Tanasie G, Tatu CS, Panaitescu C, Paunescu V: Telocytes within human skeletal muscle stem cell niche. J Cell Mol Med 2011:15:2269-2272.
  32. Suciu LC, Popescu BO, Kostin S, Popescu LM: Platelet-derived growth factor receptor-β-positive telocytes in skeletal muscle interstitium. J Cell Mol Med 2012:16:701-707.
  33. Hatta K, Huang ML, Weisel RD, Li RK: Culture of rat endometrial telocytes. J Cell Mol Med 2012:16:1392-1396.
  34. Cretoiu SM, Simionescu AA, Caravia L, Curici A, Cretoiu D, Popescu LM: Complex effects of imatinib on spontaneous and oxytocin-induced contractions in human non-pregnant myometrium. Acta Physiol Hung 2011:98:329-338.
  35. Rosenbaum ST, Svalo J, Nielsen K, Larsen T, Jorgensen JC, Bouchelouche P. Immunolocalization and expression of small-conductance calcium-activated potassium channels in human myometrium. J Cell Mol Med 2012:16:3001-3008.
  36. Creţoiu SM, Creţoiu D, Popescu LM: Human myometrium - the ultrastructural 3D network of telocytes. J Cell Mol Med 2012:16:2844-2849.
  37. Cretoiu SM, Cretoiu D, Marin A, Radu BM, Popescu LM: Telocytes: ultrastructural, immunohistochemical and electrophysiological characteristics in human myometrium. Reprod Camb Engl 2013:145:357-370.
  38. Campeanu RA, Radu SM, Cretoiu SM, Banciu DD, Banciu A, Cretoiu D, Popescu LM: Near-infrared low-level laser stimulation of telocytes from human myometrium. Lasers Med Sci 2014:29:1867-1874.
  39. Gevaert T, De Vos R, Van Der Aa F, Joniau S, van den Oord J, Roskams T, De Ridder D: Identification of telocytes in the upper lamina propria of the human urinary tract. J Cell Mol Med 2012:16:2085-2093.
  40. Zheng Y, Zhu T, Lin M, Wu D, Wang X: Telocytes in the urinary system. J Transl Med 2012:10:188.
  41. Qi G, Lin M, Xu M, Manole CG, Wang X, Zhu T. Telocytes in the human kidney cortex. J Cell Mol Med 2012:16:3116-3122.
  42. Cantarero I, Luesma MJ, Junquera C: The primary cilium of telocytes in the vasculature: electron microscope imaging. J Cell Mol Med 2011:15:2594-2600.
  43. Li H, Lu S, Liu H, Ge J, Zhang H: Scanning electron microscope evidence of telocytes in vasculature. J Cell Mol Med 2014:18:1486-1489.
  44. Hinescu ME, Gherghiceanu M, Suciu L, Popescu LM: Telocytes in pleura: two- and three-dimensional imaging by transmission electron microscopy. Cell Tissue Res 2011:343:389-397.
  45. Chen X, Zheng Y, Manole CG, Wang X, Wang Q: Telocytes in human oesophagus. J Cell Mol Med 2013:17:1506-1512.
  46. Rusu MC, Nicolescu MI, Jianu AM, Lighezan R, Manoiu VS, Paduraru D: Esophageal telocytes and hybrid morphologies. Cell Biol Int 2012:36:1079-1088.
  47. Cantarero Carmona I, Luesma Bartolomé MJ, Junquera Escribano C: Identification of telocytes in the lamina propria of rat duodenum: transmission electron microscopy. J Cell Mol Med 2011:15:26-30.
  48. Cretoiu D, Cretoiu SM, Simionescu AA, Popescu LM: Telocytes, a distinct type of cell among the stromal cells present in the lamina propria of jejunum. Histol Histopathol 2012:27:1067-1078.
  49. Popescu BO, Gherghiceanu M, Kostin S, Ceafalan L, Popescu LM: Telocytes in meninges and choroid plexus. Neurosci Lett 2012:516:265-269.
  50. Díaz-Flores L, Gutiérrez R, Sáez FJ, Díaz-Flores L, Jr Madrid JF: Telocytes in neuromuscular spindles.J Cell Mol Med 2013:17:457-465.
  51. Nicolescu MI, Bucur A, Dinca O, Rusu MC, Popescu LM: Telocytes in parotid glands. Anat Rec (Hoboken) 2012:295:378-385.
  52. Rusu MC, Pop F, Hostiuc S, Dermengiu D, Lala AI, Ion DA, Manoiu VS, Mirancea N. The human trigeminal ganglion: c-kit positive neurons and interstitial cells. Ann Anat 2011:193:403-411.
  53. Corradi LS, Jesus MM, Fochi RA, Vilamaior PS, Justulin LA Jr, Goes RM, Felisbino SL, Taboga SR: Structural and ultrastructural evidence for telocytes in prostate stroma. J. Cell Mol Med 2013:17:398-406.
  54. Xiao J, Wang F, Liu Z, Yang C: Telocytes in liver: electron microscopic and immunofluorescent evidence. J Cell Mol Med 2013:17:1537-1542.
  55. Luesma MJ, Gherghiceanu M, Popescu LM: Telocytes and stem cells in limbus and uvea of mouse eye. J Cell Mol Med 2013:17:1016-1024.
  56. Gherghiceanu M, Popescu LM: Cardiomyocyte precursors and telocytes in epicardial stem cell niche: electron microscope images. J Cell Mol Med 2010:14:871-877.
  57. Gherghiceanu M, Popescu LM: Cardiac telocytes - their junctions and functional implications. Cell Tissue Res 2012:348:265-279.
  58. Manetti M, Rosa I, Messerini L, Guiducci S, Matucci-Cerinic M, Ibba-Manneschi L: A loss of telocytes accompanies fibrosis of multiple organs in systemic sclerosis. J Cell Mol Med 2014:18:253-262.
  59. Manetti M, Guiducci S, Ruffo M, Rosa I, Faussone-Pellegrini MS, Matucci-Cerinic M, Ibba-Manneschi L: Evidence for progressive reduction and loss of telocytes in the dermal cellular network of systemic sclerosis. J Cell Mol Med 2013:17:482-496.
  60. Li L, Lin M, Li L, Wang R, Zhang C, Qi G, Xu M, Rong R, Zhu T: Renal telocytes contribute to the repair of ischemically injured renal tubules. J Cell Mol Med 2014:18:1144-1156.
  61. Manole CG, Cismaşiu V, Gherghiceanu M, Popescu LM: Experimental acute myocardial infarction: telocytes involvement in neo-angiogenesis. J Cell Mol Med 2011:15:2284-2296.
  62. Zhao B, Chen S, Liu J, Yuan Z, Qi X, Qin J, Zheng X, Shen X, Yu Y, Qnin TJ, Chan JY, Cai D. Cardiac telocytes were decreased during myocardial infarction and their therapeutic effects for ischaemic heart in rat. J Cell Mol Med 2013:17:123-133.
  63. Zhao B, Liao Z, Chen S, Yuan Z, Yilin C, Lee KK, Qi X, Shen X, Zheng X, Quinn T, Cai D. Intramyocardial transplantation of cardiac telocytes decreases myocardial infarction and improves post-infarcted cardiac function in rats. J Cell Mol Med 2014:18:780-789.
  64. Zheng Y, Zhang M, Qian M, Wang L, Cismasiu VB, Bai C, Popescu LM, Wang X: Genetic comparison of mouse lung telocytes with mesenchymal stem cells and fibroblasts. J Cell Mol Med 2013:17:567-577.
  65. Wang F, Song Y, Bei Y, Zhao Y, Xiao J, Yang C: Telocytes in liver regeneration: possible roles. J Cell Mol Med 2014:18:1720-1726.
  66. Vannucchi MG, Traini C, Manetti M, Ibba-Manneschi L, Faussone-Pellegrini MS: Telocytes express PDGFRα in the human gastrointestinal tract. J Cell Mol Med 2013:17:1099-1108.
  67. Milona A, Owen BM, van Mil S, Dormann D, Mataki C, Boudijelal M, Cairns W, Schoonjans K, Milligan S, Parker M, White R, Williamson C: The normal mechanisms of pregnancy-induced liver growth are not maintained in mice lacking the bile acid sensor Fxr. Am J Physiol Gastrointest Liver Physiol 2010:298:G151-158.
  68. Dai G, Bustamante JJ, Zou Y, Myronovych A, Bao Q, Kumar S, Soares MJ: Maternal hepatic growth response to pregnancy in the mouse. Exp Biol Med (Maywood) 2011:236:1322-1332.
  69. Zou Y, Hu M, Bao Q, Chan JY, Dai G: Nrf2 participates in regulating maternal hepatic adaptations to pregnancy. J Cell Sci 2013:126:1618-1625.
  70. Bani D, Nistri S: New insights into the morphogenic role of stromal cells and their relevance for regenerative medicine. lessons from the heart. J Cell Mol Med 2014:18:363-370.

Author Contacts

Professor Changqing Yang and Dr. Junjie Xiao

Division of Gastroenterology and Hepatology, Digestive Disease Institute, Tongji

Hospital, Tongji University School of Medicine, 389 Xin Cun Road, Shanghai 200065

(China); and Regeneration and Ageing Lab, Experimental Center of Life Sciences, School

of Life Science, Shanghai University, 333 Nan Chen Road, Shanghai 200444 (China)

E-Mail changqingyang_tj@hotmail.com and E-Mail junjiexiao@live.cn


Article / Publication Details

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Abstract of Original Paper

Accepted: February 20, 2015
Published online: May 04, 2015
Issue release date: May 2015

Number of Print Pages: 9
Number of Figures: 4
Number of Tables: 0

ISSN: 1015-8987 (Print)
eISSN: 1421-9778 (Online)

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References

  1. Kandilis AN, Koskinas J, Tiniakos DG, Nikiteas N, Perrea DN: Liver regeneration: focus on cell types and topographic differences. Eur Surg Res 2010:44:1-12.
  2. Itoh T, Miyajima A: Liver regeneration by stem/progenitor cells. Hepatol Baltim Md 2014:59:1617-1626.
  3. Duncan AW, Soto-Gutierrez A: Liver repopulation and regeneration: new approaches to old questions. Curr Opin Organ Transplant 2013:18:197-202.
  4. Little SA, Jarnagin WR, DeMatteo RP, Blumgart LH, Fong Y: Diabetes is associated with increased perioperative mortality but equivalent long-term outcome after hepatic resection for colorectal cancer. J Gastrointest Surg 2002:6:88-94.
  5. Wang DW, Yin YM, Yao YM: Advances in the management of acute liver failure. World J Gastroenterol 2013:19:7069-7077.
  6. Serenari M, Cescon M, Cucchetti A, Pinna AD: Liver function impairment in liver transplantation and after extended hepatectomy. World J Gastroenterol 2013:19:7922-7929.
  7. Bucher NL, Swaffield MN, Ditroia JF: The influence of upon the incorporation of thymidine-2C14 into the DNA of regenerating rat liver. Cancer Res 1964:24:509-512.
  8. Iakova P, Awad SS, Timchenko NA: Aging reduces proliferative capacities of liver by switching pathways of C/EBPalpha growth arrest. Cell 2003:113:495-506.
  9. Timchenko LT, Salisbury E, Wang GL, Nguyen H, Albrecht JH, Hershey JW, Timchenko NA: Age-specific CUGBP1-eIF2 complex increases translation of CCAAT/enhancer-binding protein beta in old liver. J Biol Chem 2006:281:32806-32819.
  10. Mesbah MM, Baldwin RL: Effects of diet, pregnancy, and lactation on enzyme activities and gluconeogenesis in ruminant liver. J Dairy Sci 1983:66:783-788.
  11. Hollister A, Okubara P, Watson JG, Chaykin S: Reproduction in mice: liver enlargement in mice during pregnancy and lactation. Life Sci 1987:40:11-18.
  12. Dickmann LJ, Tay S, Senn TD, Zhang H, Visone A, Unadkat JD, Hebert MF, Isoherranen N: Changes in maternal liver Cyp2c and Cyp2d expression and activity during rat pregnancy. Biochem Pharmacol 2008:75:1677-1687.
  13. Bustamante JJ, Copple BL, Soares MJ, Dai G: Gene profiling of maternal hepatic adaptations to pregnancy. Liver Int 2010:30:406-415.
  14. Gielchinsky Y, Laufer N, Weitman E, Abramovitch R, Grabot Z, Bergman Y, Pikarsky E: Pregnancy restores the regenerative capacity of the aged liver via activation of an mTORC1-controlled hyperplasia/hypertrophy switch. Genes Dev 2010:24:543-548.
  15. Popescu LM, Faussone-Pellegrini MS: TELOCYTES - a case of serendipity: the winding way from Interstitial Cells of Cajal (ICC), via Interstitial Cajal-Like Cells (ICLC) to TELOCYTES. J Cell Mol Med 2010:14:729-740.
  16. Cretoiu D, Hummel E, Zimmermann H, Gherghiceanu M, Popescu LM: Human cardiac telocytes: 3D imaging by FIB-SEM tomography. J Cell Mol Med 2014:18:2157-2164.
  17. Kostin S: Myocardial telocytes: a specific new cellular entity. J Cell Mol Med 2010:14:1917-1921.
  18. Faussone-Pellegrini MS, Bani D: Relationships between telocytes and cardiomyocytes during pre- and post-natal life. J Cell Mol Med 2010:14:1061-1063.
  19. Popescu LM, Manole CG, Geherghiceanu M, Ardelean A, Nicolescu MI, Hinescu ME, Kostin S. Telocytes in human epicardium. J Cell Mol Med 2010:14:2085-2093.
  20. Gherghiceanu M, Manole CG, Popescu LM: Telocytes in endocardium: electron microscope evidence. J Cell Mol Med 2010:14:2330-2334.
  21. Yang Y, Sun W, Wu SM, Xiao J, Kong X: Telocytes in human heart valves. J Cell Mol Med 2014:18:759-765.
  22. Zheng Y, Li H, Manole CG, Sun A, Ge J, Wang X: Telocytes in trachea and lungs. J Cell Mol Med 2011:15:2262-2268.
  23. Popescu LM, Gherghiceanu M, Suciu LC, Manole CG, Hinescu ME: Telocytes and putative stem cells in the lungs: electron microscopy, electron tomography and laser scanning microscopy. Cell Tissue Res 2011:345:391-403.
  24. Rusu MC, Jianu AM, Mirancea N, Didilescu AC, Manoiu VS, Paduraru D: Tracheal telocytes. J Cell Mol Med 2012:16:401-405.
  25. Suciu L, Popescu LM, Gherghiceanu M, Regalia T, Nicolescu MI, Hinescu ME, Faussone-Pellegrini MS: Telocytes in human term placenta: morphology and phenotype. Cells Tissues Organs 2010:192:325-339.
  26. Nicolescu MI, Popescu LM: Telocytes in the interstitium of human exocrine pancreas: ultrastructural evidence. Pancreas 2012:41:949-956.
  27. Bosco C, Díaz E, Gutiérrez R, González J, Pérez J: Ganglionar nervous cells and telocytes in the pancreas of Octodon degus: extra and intrapancreatic ganglionar cells and telocytes in the degus. Auton Neurosci Basic Clin 2013:177:224-230.
  28. Rusu MC, Mirancea N, Manoiu VS, Valcu M, Nicolescu MI, Paduraru D: Skin telocytes. Ann Anat 2012:194:359-367.
  29. Ceafalan L, Gherghiceanu M, Popescu L M, Simionescu O: Telocytes in human skin-are they involved in skin regeneration? J Cell Mol Med 2012:16:1405-1420.
  30. Popescu LM, Manole E, Serboiu CS, Manole CG, Suciu LC, Gherghiceanu M, Popescu BO: Identification of telocytes in skeletal muscle interstitium: implication for muscle regeneration. J Cell Mol Med 2011:15:1379-1392.
  31. Bojin FM, Gavriliuc OI, Cristea MI, Tanasie G, Tatu CS, Panaitescu C, Paunescu V: Telocytes within human skeletal muscle stem cell niche. J Cell Mol Med 2011:15:2269-2272.
  32. Suciu LC, Popescu BO, Kostin S, Popescu LM: Platelet-derived growth factor receptor-β-positive telocytes in skeletal muscle interstitium. J Cell Mol Med 2012:16:701-707.
  33. Hatta K, Huang ML, Weisel RD, Li RK: Culture of rat endometrial telocytes. J Cell Mol Med 2012:16:1392-1396.
  34. Cretoiu SM, Simionescu AA, Caravia L, Curici A, Cretoiu D, Popescu LM: Complex effects of imatinib on spontaneous and oxytocin-induced contractions in human non-pregnant myometrium. Acta Physiol Hung 2011:98:329-338.
  35. Rosenbaum ST, Svalo J, Nielsen K, Larsen T, Jorgensen JC, Bouchelouche P. Immunolocalization and expression of small-conductance calcium-activated potassium channels in human myometrium. J Cell Mol Med 2012:16:3001-3008.
  36. Creţoiu SM, Creţoiu D, Popescu LM: Human myometrium - the ultrastructural 3D network of telocytes. J Cell Mol Med 2012:16:2844-2849.
  37. Cretoiu SM, Cretoiu D, Marin A, Radu BM, Popescu LM: Telocytes: ultrastructural, immunohistochemical and electrophysiological characteristics in human myometrium. Reprod Camb Engl 2013:145:357-370.
  38. Campeanu RA, Radu SM, Cretoiu SM, Banciu DD, Banciu A, Cretoiu D, Popescu LM: Near-infrared low-level laser stimulation of telocytes from human myometrium. Lasers Med Sci 2014:29:1867-1874.
  39. Gevaert T, De Vos R, Van Der Aa F, Joniau S, van den Oord J, Roskams T, De Ridder D: Identification of telocytes in the upper lamina propria of the human urinary tract. J Cell Mol Med 2012:16:2085-2093.
  40. Zheng Y, Zhu T, Lin M, Wu D, Wang X: Telocytes in the urinary system. J Transl Med 2012:10:188.
  41. Qi G, Lin M, Xu M, Manole CG, Wang X, Zhu T. Telocytes in the human kidney cortex. J Cell Mol Med 2012:16:3116-3122.
  42. Cantarero I, Luesma MJ, Junquera C: The primary cilium of telocytes in the vasculature: electron microscope imaging. J Cell Mol Med 2011:15:2594-2600.
  43. Li H, Lu S, Liu H, Ge J, Zhang H: Scanning electron microscope evidence of telocytes in vasculature. J Cell Mol Med 2014:18:1486-1489.
  44. Hinescu ME, Gherghiceanu M, Suciu L, Popescu LM: Telocytes in pleura: two- and three-dimensional imaging by transmission electron microscopy. Cell Tissue Res 2011:343:389-397.
  45. Chen X, Zheng Y, Manole CG, Wang X, Wang Q: Telocytes in human oesophagus. J Cell Mol Med 2013:17:1506-1512.
  46. Rusu MC, Nicolescu MI, Jianu AM, Lighezan R, Manoiu VS, Paduraru D: Esophageal telocytes and hybrid morphologies. Cell Biol Int 2012:36:1079-1088.
  47. Cantarero Carmona I, Luesma Bartolomé MJ, Junquera Escribano C: Identification of telocytes in the lamina propria of rat duodenum: transmission electron microscopy. J Cell Mol Med 2011:15:26-30.
  48. Cretoiu D, Cretoiu SM, Simionescu AA, Popescu LM: Telocytes, a distinct type of cell among the stromal cells present in the lamina propria of jejunum. Histol Histopathol 2012:27:1067-1078.
  49. Popescu BO, Gherghiceanu M, Kostin S, Ceafalan L, Popescu LM: Telocytes in meninges and choroid plexus. Neurosci Lett 2012:516:265-269.
  50. Díaz-Flores L, Gutiérrez R, Sáez FJ, Díaz-Flores L, Jr Madrid JF: Telocytes in neuromuscular spindles.J Cell Mol Med 2013:17:457-465.
  51. Nicolescu MI, Bucur A, Dinca O, Rusu MC, Popescu LM: Telocytes in parotid glands. Anat Rec (Hoboken) 2012:295:378-385.
  52. Rusu MC, Pop F, Hostiuc S, Dermengiu D, Lala AI, Ion DA, Manoiu VS, Mirancea N. The human trigeminal ganglion: c-kit positive neurons and interstitial cells. Ann Anat 2011:193:403-411.
  53. Corradi LS, Jesus MM, Fochi RA, Vilamaior PS, Justulin LA Jr, Goes RM, Felisbino SL, Taboga SR: Structural and ultrastructural evidence for telocytes in prostate stroma. J. Cell Mol Med 2013:17:398-406.
  54. Xiao J, Wang F, Liu Z, Yang C: Telocytes in liver: electron microscopic and immunofluorescent evidence. J Cell Mol Med 2013:17:1537-1542.
  55. Luesma MJ, Gherghiceanu M, Popescu LM: Telocytes and stem cells in limbus and uvea of mouse eye. J Cell Mol Med 2013:17:1016-1024.
  56. Gherghiceanu M, Popescu LM: Cardiomyocyte precursors and telocytes in epicardial stem cell niche: electron microscope images. J Cell Mol Med 2010:14:871-877.
  57. Gherghiceanu M, Popescu LM: Cardiac telocytes - their junctions and functional implications. Cell Tissue Res 2012:348:265-279.
  58. Manetti M, Rosa I, Messerini L, Guiducci S, Matucci-Cerinic M, Ibba-Manneschi L: A loss of telocytes accompanies fibrosis of multiple organs in systemic sclerosis. J Cell Mol Med 2014:18:253-262.
  59. Manetti M, Guiducci S, Ruffo M, Rosa I, Faussone-Pellegrini MS, Matucci-Cerinic M, Ibba-Manneschi L: Evidence for progressive reduction and loss of telocytes in the dermal cellular network of systemic sclerosis. J Cell Mol Med 2013:17:482-496.
  60. Li L, Lin M, Li L, Wang R, Zhang C, Qi G, Xu M, Rong R, Zhu T: Renal telocytes contribute to the repair of ischemically injured renal tubules. J Cell Mol Med 2014:18:1144-1156.
  61. Manole CG, Cismaşiu V, Gherghiceanu M, Popescu LM: Experimental acute myocardial infarction: telocytes involvement in neo-angiogenesis. J Cell Mol Med 2011:15:2284-2296.
  62. Zhao B, Chen S, Liu J, Yuan Z, Qi X, Qin J, Zheng X, Shen X, Yu Y, Qnin TJ, Chan JY, Cai D. Cardiac telocytes were decreased during myocardial infarction and their therapeutic effects for ischaemic heart in rat. J Cell Mol Med 2013:17:123-133.
  63. Zhao B, Liao Z, Chen S, Yuan Z, Yilin C, Lee KK, Qi X, Shen X, Zheng X, Quinn T, Cai D. Intramyocardial transplantation of cardiac telocytes decreases myocardial infarction and improves post-infarcted cardiac function in rats. J Cell Mol Med 2014:18:780-789.
  64. Zheng Y, Zhang M, Qian M, Wang L, Cismasiu VB, Bai C, Popescu LM, Wang X: Genetic comparison of mouse lung telocytes with mesenchymal stem cells and fibroblasts. J Cell Mol Med 2013:17:567-577.
  65. Wang F, Song Y, Bei Y, Zhao Y, Xiao J, Yang C: Telocytes in liver regeneration: possible roles. J Cell Mol Med 2014:18:1720-1726.
  66. Vannucchi MG, Traini C, Manetti M, Ibba-Manneschi L, Faussone-Pellegrini MS: Telocytes express PDGFRα in the human gastrointestinal tract. J Cell Mol Med 2013:17:1099-1108.
  67. Milona A, Owen BM, van Mil S, Dormann D, Mataki C, Boudijelal M, Cairns W, Schoonjans K, Milligan S, Parker M, White R, Williamson C: The normal mechanisms of pregnancy-induced liver growth are not maintained in mice lacking the bile acid sensor Fxr. Am J Physiol Gastrointest Liver Physiol 2010:298:G151-158.
  68. Dai G, Bustamante JJ, Zou Y, Myronovych A, Bao Q, Kumar S, Soares MJ: Maternal hepatic growth response to pregnancy in the mouse. Exp Biol Med (Maywood) 2011:236:1322-1332.
  69. Zou Y, Hu M, Bao Q, Chan JY, Dai G: Nrf2 participates in regulating maternal hepatic adaptations to pregnancy. J Cell Sci 2013:126:1618-1625.
  70. Bani D, Nistri S: New insights into the morphogenic role of stromal cells and their relevance for regenerative medicine. lessons from the heart. J Cell Mol Med 2014:18:363-370.
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