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Original Paper

Free Access

Autologous Adipose Tissue Graft to Treat Hypertensive Leg Ulcer: A Pilot Study

Chopinaud M.a · Labbé D.b · Creveuil C.c · Marc M.a · Bénateau H.b · Mourgeon B.c · Chopinaud E.e · Veyssière A.b · Dompmartin A.b, d

Author affiliations

Departments of aDermatology and bMaxillofacial and Plastic Surgery, cBiostatistics and Clinical Research Unit, and dBioconnect Laboratory EA 4652, Caen University Hospital, Caen, France; eUniversity of Warwick, Coventry, UK

Corresponding Author

Dr. Marianne Chopinaud

Department of Dermatology, Caen University Hospital

Avenue Côte de Nacre

FR-14000 Caen (France)

E-Mail mariannechopinaud@hotmail.com

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Dermatology 2017;233:234-241

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Abstract

Background: Adipose tissue is an abundant source of mesenchymal stem cells, called adipose-derived stem cells, which have anti-inflammatory and trophic effects to enhance overall tissue repair. Objective: To determine the healing effects of autologous adipose tissue graft on hypertensive leg ulcers. Methods: Prospective pilot study in 1 French dermatology department. Ten patients with a hypertensive leg ulcer were enrolled from April 2013 to June 2015. The primary end point was the wound closure rate at each follow-up visit. The secondary end points were wound characteristics, pain assessment and adverse events. Results: One patient, the only smoker, was lost to follow-up at month 5 (M5). For the 9 non-smokers, wound surfaces constantly and significantly decreased: the median wound closure rate was 73.2% at M3 and 93.1% at M6, p < 0.001. The median wound closure rate of the 10 patients was 63.2% at M3, p < 0.001. Percentages of fibrin and necrosis decreased, granulation tissue increased significantly. Pain rapidly and significantly decreased. No recurrence or adverse event was observed. Conclusion: Our data suggest that autologous adipose tissue grafting induces pain relief and promotes wound healing with a good skin quality. Large prospective controlled randomized studies are required to confirm these results.

© 2017 S. Karger AG, Basel


References

  1. Martorell F: Las úlceras supramaleolares por arteriolitis de las grandes hipertensas. Actas Reuniones Científicas Cuerpo Fac Inst Policlínico Barc 1945;1:6-9.
  2. Hines EA Jr, Farber EM: Ulcer of the leg due to arteriolosclerosis and ischemia occurring in the presence of hypertensive disease (hypertensive-ischemic ulcers): a preliminary report. J Lab Clin Med 1947;32:323.
  3. Vuerstaek JDD, Reeder SWI, Henquet CJM, Neumann HAM: Arteriolosclerotic ulcer of Martorell. J Eur Acad Dermatol Venereol 2010;24:867-874.
  4. Hafner J, Nobbe S, Partsch H, Läuchli S, Mayer D, Amann-Vesti B, et al: Martorell hypertensive ischemic leg ulcer: a model of ischemic subcutaneous arteriolosclerosis. Arch Dermatol 2010;146:961-968.
  5. Henderson CA, Highet AS, Lane SA, Hall R: Arterial hypertension causing leg ulcers. Clin Exp Dermatol 1995;20:107-114.
  6. Dagregorio G, Guillet G: A retrospective review of 20 hypertensive leg ulcers treated with mesh skin grafts. J Eur Acad Dermatol Venereol 2006;20:166-169.
  7. Senet P, Vicaut E, Beneton N, Debure C, Lok C, Chosidow O: Topical treatment of hypertensive leg ulcers with platelet-derived growth factor-BB: a randomized controlled trial. Arch Dermatol 2011;147:926-930.
  8. Carre D, Dompmartin A, Gislard A, Loree S, Faguer K, Verneuil L, et al: Benefit of topical steroids in necrotic angiodermatitis (in French). Ann Dermatol Vénéréol 2003;130:547-548.
  9. Chaby G, Senet P, Vaneau M, Martel P, Guillaume J-C, Meaume S, et al: Dressings for acute and chronic wounds: a systematic review. Arch Dermatol 2007;143:1297-1304.
  10. Lazareth I, Priollet P: Necrotic angiodermatitis: treatment by early cutaneous grafts (in French). Ann Dermatol Vénéréol 1995;122:575-578.
  11. Baer PC: Adipose-derived mesenchymal stromal/stem cells: an update on their phenotype in vivo and in vitro. World J Stem Cells 2014;6:256-265.
  12. Casteilla L, Planat-Benard V, Laharrague P, Cousin B: Adipose-derived stromal cells: their identity and uses in clinical trials, an update. World J Stem Cells 2011;3:25-33.
  13. Hassan WU, Greiser U, Wang W: Role of adipose-derived stem cells in wound healing. Wound Repair Regen Off Publ Wound Heal Soc Eur Tissue Repair Soc 2014;22:313-325.
  14. Teng M, Huang Y, Zhang H: Application of stem cells in wound healing - an update. Wound Repair Regen Off Publ Wound Heal Soc Eur Tissue Repair Soc 2014;22:151-160.
  15. Tsuji W, Rubin JP, Marra KG: Adipose-derived stem cells: implications in tissue regeneration. World J Stem Cells 2014;6:312-321.
  16. Coleman SR: Structural fat grafting: more than a permanent filler. Plast Reconstr Surg 2006;118:108S-120S.
  17. Coleman WP 3rd: Autologous fat transplantation. Plast Reconstr Surg 1991;88:736.
  18. Coleman SR: Hand rejuvenation with structural fat grafting. Plast Reconstr Surg 2002;110:1731-1744; discussion 1745-1747.
  19. Coleman SR: Structural fat grafts: the ideal filler? Clin Plast Surg 2001;28:111-119.
  20. Nguyen PSA, Desouches C, Gay AM, Hautier A, Magalon G: Development of micro-injection as an innovative autologous fat graft technique: the use of adipose tissue as dermal filler. J Plast Reconstr Aesthetic Surg 2012;65:1692-1699.
  21. Collet C, Laversanne S, Haen P, Derkenne R, Brignol L, Thiéry G: Micro-re-injection of autologous fat (in French). Rev Stomatol Chir Maxillo-Faciale Chir Orale 2013;114:381-386.
  22. Laplaud A-L, Blaizot X, Gaillard C, Morice A, Lebreuilly I, Clément C, et al: Wound debridement: comparative reliability of three methods for measuring fibrin percentage in chronic wounds. Wound Repair Regen Off Publ Wound Heal Soc Eur Tissue Repair Soc 2010;18:13-20.
  23. Nicol C, Le Fourn B, Milpied B: Use of Coleman's lipostructure for post-scleroderma facial hemiatrophy (in French). Ann Dermatol Vénéréol 2007;134:384-385.
  24. Sarfati I, Ihrai T, Kaufman G, Nos C, Clough KB: Adipose-tissue grafting to the post-mastectomy irradiated chest wall: preparing the ground for implant reconstruction. J Plast Reconstr Aesthetic Surg 2011;64:1161-1166.
  25. Rigotti G, Marchi A, Galiè M, Baroni G, Benati D, Krampera M, et al: Clinical treatment of radiotherapy tissue damage by lipoaspirate transplant: a healing process mediated by adipose-derived adult stem cells. Plast Reconstr Surg 2007;119:1409-1422; discussion 1423-1424.
  26. Mojallal A, Lequeux C, Shipkov C, Breton P, Foyatier J-L, Braye F, et al: Improvement of skin quality after fat grafting: clinical observation and an animal study. Plast Reconstr Surg 2009;124:765-774.
  27. Kirsner RS, Falanga V, Eaglstein WH: The biology of skin grafts. Skin grafts as pharmacologic agents. Arch Dermatol 1993;129:481-483.
  28. McDaniel JC, Browning KK: Smoking, chronic wound healing, and implications for evidence-based practice. J Wound Ostomy Continence Nurs 2014;41:415-423; quiz E1-E2.
  29. Whiteford L: Nicotine, CO and HCN: the detrimental effects of smoking on wound healing. Br J Community Nurs 2003;8:S22-S26.
  30. Ojeh N, Pastar I, Tomic-Canic M, Stojadinovic O: Stem cells in skin regeneration, wound healing, and their clinical applications. Int J Mol Sci 2015;16:25476-25501.
  31. Friedenstein AJ, Petrakova KV, Kurolesova AI, Frolova GP: Heterotopic of bone marrow. Analysis of precursor cells for osteogenic and hematopoietic tissues. Transplantation 1968;6:230-247.
  32. Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD, et al: Multilineage potential of adult human mesenchymal stem cells. Science 1999;284:143-147.
  33. Lataillade JJ, Doucet C, Bey E, Carsin H, Huet C, Clairand I, et al: New approach to radiation burn treatment by dosimetry-guided surgery combined with autologous mesenchymal stem cell therapy. Regen Med 2007;2:785-794.
  34. Yoshimura K, Suga H, Eto H: Adipose-derived stem/progenitor cells: roles in adipose tissue remodeling and potential use for soft tissue augmentation. Regen Med 2009;4:265-273.
  35. Cherubino M, Rubin JP, Miljkovic N, Kelmendi-Doko A, Marra KG: Adipose-derived stem cells for wound healing applications. Ann Plast Surg 2011;66:210-215.
  36. Gosain A, DiPietro LA: Aging and wound healing. World J Surg 2004;28:321-326.

Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: April 04, 2017
Accepted: June 05, 2017
Published online: July 27, 2017
Issue release date: October 2017

Number of Print Pages: 8
Number of Figures: 6
Number of Tables: 2

ISSN: 1018-8665 (Print)
eISSN: 1421-9832 (Online)

For additional information: https://www.karger.com/DRM

References

  1. Martorell F: Las úlceras supramaleolares por arteriolitis de las grandes hipertensas. Actas Reuniones Científicas Cuerpo Fac Inst Policlínico Barc 1945;1:6-9.
  2. Hines EA Jr, Farber EM: Ulcer of the leg due to arteriolosclerosis and ischemia occurring in the presence of hypertensive disease (hypertensive-ischemic ulcers): a preliminary report. J Lab Clin Med 1947;32:323.
  3. Vuerstaek JDD, Reeder SWI, Henquet CJM, Neumann HAM: Arteriolosclerotic ulcer of Martorell. J Eur Acad Dermatol Venereol 2010;24:867-874.
  4. Hafner J, Nobbe S, Partsch H, Läuchli S, Mayer D, Amann-Vesti B, et al: Martorell hypertensive ischemic leg ulcer: a model of ischemic subcutaneous arteriolosclerosis. Arch Dermatol 2010;146:961-968.
  5. Henderson CA, Highet AS, Lane SA, Hall R: Arterial hypertension causing leg ulcers. Clin Exp Dermatol 1995;20:107-114.
  6. Dagregorio G, Guillet G: A retrospective review of 20 hypertensive leg ulcers treated with mesh skin grafts. J Eur Acad Dermatol Venereol 2006;20:166-169.
  7. Senet P, Vicaut E, Beneton N, Debure C, Lok C, Chosidow O: Topical treatment of hypertensive leg ulcers with platelet-derived growth factor-BB: a randomized controlled trial. Arch Dermatol 2011;147:926-930.
  8. Carre D, Dompmartin A, Gislard A, Loree S, Faguer K, Verneuil L, et al: Benefit of topical steroids in necrotic angiodermatitis (in French). Ann Dermatol Vénéréol 2003;130:547-548.
  9. Chaby G, Senet P, Vaneau M, Martel P, Guillaume J-C, Meaume S, et al: Dressings for acute and chronic wounds: a systematic review. Arch Dermatol 2007;143:1297-1304.
  10. Lazareth I, Priollet P: Necrotic angiodermatitis: treatment by early cutaneous grafts (in French). Ann Dermatol Vénéréol 1995;122:575-578.
  11. Baer PC: Adipose-derived mesenchymal stromal/stem cells: an update on their phenotype in vivo and in vitro. World J Stem Cells 2014;6:256-265.
  12. Casteilla L, Planat-Benard V, Laharrague P, Cousin B: Adipose-derived stromal cells: their identity and uses in clinical trials, an update. World J Stem Cells 2011;3:25-33.
  13. Hassan WU, Greiser U, Wang W: Role of adipose-derived stem cells in wound healing. Wound Repair Regen Off Publ Wound Heal Soc Eur Tissue Repair Soc 2014;22:313-325.
  14. Teng M, Huang Y, Zhang H: Application of stem cells in wound healing - an update. Wound Repair Regen Off Publ Wound Heal Soc Eur Tissue Repair Soc 2014;22:151-160.
  15. Tsuji W, Rubin JP, Marra KG: Adipose-derived stem cells: implications in tissue regeneration. World J Stem Cells 2014;6:312-321.
  16. Coleman SR: Structural fat grafting: more than a permanent filler. Plast Reconstr Surg 2006;118:108S-120S.
  17. Coleman WP 3rd: Autologous fat transplantation. Plast Reconstr Surg 1991;88:736.
  18. Coleman SR: Hand rejuvenation with structural fat grafting. Plast Reconstr Surg 2002;110:1731-1744; discussion 1745-1747.
  19. Coleman SR: Structural fat grafts: the ideal filler? Clin Plast Surg 2001;28:111-119.
  20. Nguyen PSA, Desouches C, Gay AM, Hautier A, Magalon G: Development of micro-injection as an innovative autologous fat graft technique: the use of adipose tissue as dermal filler. J Plast Reconstr Aesthetic Surg 2012;65:1692-1699.
  21. Collet C, Laversanne S, Haen P, Derkenne R, Brignol L, Thiéry G: Micro-re-injection of autologous fat (in French). Rev Stomatol Chir Maxillo-Faciale Chir Orale 2013;114:381-386.
  22. Laplaud A-L, Blaizot X, Gaillard C, Morice A, Lebreuilly I, Clément C, et al: Wound debridement: comparative reliability of three methods for measuring fibrin percentage in chronic wounds. Wound Repair Regen Off Publ Wound Heal Soc Eur Tissue Repair Soc 2010;18:13-20.
  23. Nicol C, Le Fourn B, Milpied B: Use of Coleman's lipostructure for post-scleroderma facial hemiatrophy (in French). Ann Dermatol Vénéréol 2007;134:384-385.
  24. Sarfati I, Ihrai T, Kaufman G, Nos C, Clough KB: Adipose-tissue grafting to the post-mastectomy irradiated chest wall: preparing the ground for implant reconstruction. J Plast Reconstr Aesthetic Surg 2011;64:1161-1166.
  25. Rigotti G, Marchi A, Galiè M, Baroni G, Benati D, Krampera M, et al: Clinical treatment of radiotherapy tissue damage by lipoaspirate transplant: a healing process mediated by adipose-derived adult stem cells. Plast Reconstr Surg 2007;119:1409-1422; discussion 1423-1424.
  26. Mojallal A, Lequeux C, Shipkov C, Breton P, Foyatier J-L, Braye F, et al: Improvement of skin quality after fat grafting: clinical observation and an animal study. Plast Reconstr Surg 2009;124:765-774.
  27. Kirsner RS, Falanga V, Eaglstein WH: The biology of skin grafts. Skin grafts as pharmacologic agents. Arch Dermatol 1993;129:481-483.
  28. McDaniel JC, Browning KK: Smoking, chronic wound healing, and implications for evidence-based practice. J Wound Ostomy Continence Nurs 2014;41:415-423; quiz E1-E2.
  29. Whiteford L: Nicotine, CO and HCN: the detrimental effects of smoking on wound healing. Br J Community Nurs 2003;8:S22-S26.
  30. Ojeh N, Pastar I, Tomic-Canic M, Stojadinovic O: Stem cells in skin regeneration, wound healing, and their clinical applications. Int J Mol Sci 2015;16:25476-25501.
  31. Friedenstein AJ, Petrakova KV, Kurolesova AI, Frolova GP: Heterotopic of bone marrow. Analysis of precursor cells for osteogenic and hematopoietic tissues. Transplantation 1968;6:230-247.
  32. Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD, et al: Multilineage potential of adult human mesenchymal stem cells. Science 1999;284:143-147.
  33. Lataillade JJ, Doucet C, Bey E, Carsin H, Huet C, Clairand I, et al: New approach to radiation burn treatment by dosimetry-guided surgery combined with autologous mesenchymal stem cell therapy. Regen Med 2007;2:785-794.
  34. Yoshimura K, Suga H, Eto H: Adipose-derived stem/progenitor cells: roles in adipose tissue remodeling and potential use for soft tissue augmentation. Regen Med 2009;4:265-273.
  35. Cherubino M, Rubin JP, Miljkovic N, Kelmendi-Doko A, Marra KG: Adipose-derived stem cells for wound healing applications. Ann Plast Surg 2011;66:210-215.
  36. Gosain A, DiPietro LA: Aging and wound healing. World J Surg 2004;28:321-326.
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