Skip to main content Skip to main navigation menu Skip to site footer

Effectiveness of conditioned medium mesenchymal stem cells intracutaneous for trophic ulcer due to morbun hansen


Link of Video Abstract:


Introduction: The facts in the field that more than 50% of chronic ulcers, especially trophic ulcers due to leprosy fail to heal with usual treatment. Stem cell therapy or one of them is conditioned medium mesenchymal stem cell is a promising therapy because of its biological and physiological processes resembling the mechanism of wound healing

Methods: This research is a clinical trial research "Open Trial" Phase 2 to see the side effects caused by the intervention. Minimum sample size of 20 respondents with trophic ulcers due to leprosy that is difficult to resolve with usual treatment. The main outcome is wound healing in terms of the length and extent of the wound. The secondary outcome is treatment toxicity 4 weeks after administration. Follow-up visits will be scheduled at 2, 4, and 12 weeks post-treatment.

Results: 24 of 27 respondents successfully followed the study until the end. Prior to intracutaneously injecting CM MSC, the mean width, length, and area of tropical ulcers in patients with Morbus Hansen were 1.1 (0.3 - 12.0) cm, 2.0 (0.5 - 9.0) cm, and 2.38 (0.25 - 108) cm square, and after intracutaneously injecting CM MSC at the first follow up were 1.0 (0 - 4.5) cm, 1.5 (0 - 8.5) cm, and 1.0 (0 - 38.25) cm. The change between the start and finish of the intervention was statistically significant (p-value 0.05). Neither systemic nor local adverse effects were observed during or up to two months after the intervention.

Conclusion: The use of intracutaneous CM MSC injection has been proven effective in accelerating the process of wound healing, especially trophic ulcers due to leprosy with side effects that are not present in this study.


  1. Santos VS, Santos LC, Lôbo LVR, Lemos LMD, Gurgel RQ, Cuevas LE. Leprosy and disability in children younger than 15 years in an endemic area of Northeast Brazil. Pediatr Infect Dis J. 2015;34(3):e44–7.
  2. Santos VS, Santos de Matos AM, Alves de Oliveira LS, Dolce de Lemos LM, Gurgel RQ, Reis FP, et al. Clinical variables associated with disability in leprosy cases in northeast Brazil. J Infect Dev Ctries. 2015;9(03):232–8.
  3. de Paula HL, de Souza CDF, Silva SR, Martins-Filho PRS, Barreto JG, Gurgel RQ, et al. Risk factors for physical disability in patients with leprosy. JAMA Dermatology. 2019;155(10):1120.
  4. van Brakel WH, Sihombing B, Djarir H, Beise K, Kusumawardhani L, Yulihane R, et al. Disability in people affected by leprosy: The role of impairment, activity, social participation, stigma and discrimination. Glob Health Action. 2012;5(1):18394.
  5. Raposo MT, Reis MC, Caminha AV de Q, Heukelbach J, Parker LA, Pastor-Valero M, et al. Grade 2 disabilities in leprosy patients from Brazil: Need for follow-up after completion of multidrug therapy. PLoS Negl Trop Dis. 2018;12(7):e0006645.
  6. UNAIDS. Global AIDS Update 2016. World Heal Organ. 2016. Available from:
  7. WHO. Global Leprosy Strategy 2016-2020. World Health Organization. 2016.
  8. Global leprosy update, 2016: accelerating reduction of disease burden. Wkly Epidemiol Rec. 2017 Sep 1;92(35):501-19.
  9. Global leprosy update, 2015: time for action, accountability and inclusion. Wkly Epidemiol Rec. 2015;91(35):405-20.
  10. Rao PN. Global leprosy strategy 2016-2020: Issues and concerns. Indian J Dermatol Venereol Leprol. 2017 Jan-Feb;83(1):4-6.
  11. Kementerian Kesehatan RI. Data dan Informasi profil Kesehatan Indonesia 2018. Jakarta: Pusat Data dan Informasi Kementerian Kesehatan; 2019.
  12. Kementerian Kesehatan RI. Hasil Utama Riset Kesehatan Dasar Tahun 2018. Jakarta: Kementrian Kesehatan Republik Indonesia; 2018.
  13. Wilder-Smith EP, Van Brakel WH. Nerve damage in leprosy and its management. Nat Clin Pract Neurol. 2008;4(12):656–63.
  14. Riyaz N, Sehgal VN. Leprosy: Trophic skin ulcers. Skinmed. 2017;15(1):45-51.
  15. Bhatt Y, Panse N, Vyas K, Patel G. Free tissue transfer for trophic ulcer complicating leprosy. Indian J Plast Surg. 2009;42(1):115.
  16. Gahalaut P, Pinto J, Pai GS, Kamath J, Joshua TV. A novel treatment for plantar ulcers in leprosy: Local superficial flaps. Lepr Rev. 2005; 76(3):220-31.
  17. Lavery LA, Vela SA, Lavery DC, Quebedeaux TL. Reducing dynamic foot pressures in high-risk diabetic subjects with foot ulcerations: A comparison of treatments. Diabetes Care. 1996; 19(8):818-21.
  18. Rao PT, Jena SK. Surgical treatment of plantar ulcers in leprosy. Int Orthop. 1986;10(2):75–8.
  19. Yolanda MM, Maria AV, Amaia FG, Marcos PB, Silvia PL, Dolores E, et al. Adult stem cell therapy in chronic wound healing. J Stem Cell Res Ther. 2014;4:1000162.
  20. Bluestein D, Javaheri A. Pressure ulcers: Prevention, evaluation, and management. Am Fam Physician. 2008;78(10):1186-94.
  21. Utomo W, Dewi YI, Abdurrasyid T. Efektifitas Nigella Sativa oil untuk mencegah terjadinya ulkus dekubitus pada pasien tirah baring lama. J Ners Indones. 2014;2(2):151–7.
  22. Vizoso FJ, Eiro N, Cid S, Schneider J, Perez-Fernandez R. Mesenchymal stem cell secretome: Toward cell-free therapeutic strategies in regenerative medicine. Int J Mol Sci. 2017;18(9):1852.
  23. Natallya F, Herwanto N, Prakoeswa C, Indramaya D, Rantam F. Effective healing of leprosy chronic plantar ulcers by application of human amniotic membrane stem cell secretome gel. Indian J Dermatol. 2019;64(3):250.
  24. Liew A, O’Brien T. Therapeutic potential for mesenchymal stem cell transplantation in critical limb ischemia. Stem Cell Res Ther. 2012;3(4):28.
  25. Bronckaers A, Hilkens P, Martens W, Gervois P, Ratajczak J, Struys T, et al. Mesenchymal stem/stromal cells as a pharmacological and therapeutic approach to accelerate angiogenesis. Pharmacol Ther. 2014;143(2):181–96.
  26. Kinnaird T, Stabile E, Burnett MS, Shou M, Lee CW, Barr S, et al. Local delivery of marrow-derived stromal cells augments collateral perfusion through paracrine mechanisms. Circulation. 2004;109(12):1543–9.
  27. Elman JS, Murray RM, Wang F, Shen K, Gao S, Conway KE, et al. Pharmacokinetics of natural and engineered secreted factors delivered by mesenchymal stromal cells. PLoS One. 2014;9(2):e89882.
  28. Duffy GP, Ahsan T, O’Brien T, Barry F, Nerem RM. Bone marrow–derived mesenchymal stem cells promote angiogenic processes in a time- and dose-dependent manner in vitro. Tissue Eng Part A. 2009;15(9):2459–70.
  29. Smith AN, Willis E, Chan VT, Muffley LA, Isik FF, Gibran NS, et al. Mesenchymal stem cells induce dermal fibroblast responses to injury. Exp Cell Res. 2010;316(1):48–54.
  30. Wan J, Xia L, Liang W, Liu Y, Cai Q. Transplantation of bone marrow-derived mesenchymal stem cells promotes delayed wound healing in diabetic rats. J Diabetes Res. 2013;2013:1–11.
  31. Griffin MD, Ritter T, Mahon BP. Immunological aspects of allogeneic mesenchymal stem cell therapies. Hum Gene Ther. 2010;21(12):1641–55.
  32. Chen L, Tredget EE, Liu C, Wu Y. Analysis of allogenicity of mesenchymal stem cells in engraftment and wound healing in mice. PLoS One. 2009;4(9):e7119.
  33. Shen Q, Chen B, Xiao Z, Zhao L, Xu X, Wan X, et al. Paracrine factors from mesenchymal stem cells attenuate epithelial injury and lung fibrosis. Mol Med Rep. 2015;11(4):2831–7.
  34. Maxson S, Lopez EA, Yoo D, Danilkovitch-Miagkova A, LeRoux MA. Concise review: Role of mesenchymal stem cells in wound repair. Stem Cells Transl Med. 2012;1(2):142–9.
  35. van Rhijn-Brouwer FCC, Gremmels H, Fledderus JO, Schuurman AH, Bonte-Mineur F, Vonk MC, et al. A randomised placebo-controlled double-blind trial to assess the safety of intramuscular administration of allogeneic mesenchymal stromal cells for digital ulcers in systemic sclerosis: the MANUS Trial protocol. BMJ Open. 2018;8(8):e020479.
  36. Dominici M, Le Blanc K, Mueller I, Slaper-Cortenbach I, Marini F, Krause DS, et al. Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy. 2006;8(4):315–7.
  37. Rajbhandari SM, Harris ND, Sutton M, Lockett C, Eaton S, Gadour M, et al. Digital imaging: an accurate and easy method of measuring foot ulcers. Diabet Med. 1999;16(4):339–42.
  38. Bhedi A, Saxena AK, Gadani R, Patel R. Digital photography and transparency-based methods for measuring wound surface area. Indian J Surg. 2013;75(2):111–4.
  39. Brandsma JW, Van Brakel WH. WHO disability grading: Operational definitions. Lepr Rev. 2003;74(4):366-73.
  40. Puri V, Venkateshwaran N, Khare N. Trophic ulcers-Practical management guidelines. Indian J Plast Surg. 2012;45(02):340–51.
  41. Sehgal VN, Prasad PVS, Kaviarasan PK, Rajan D. Trophic skin ulceration in leprosy: evaluation of the efficacy of topical phenytoin sodium zinc oxide paste. Int J Dermatol. 2014;53(7):873–8.
  42. Suryanarayan S, Budamakuntla L, Khadri SS, Sarvajnamurthy S. Efficacy of autologous platelet-rich plasma in the treatment of chronic nonhealing leg ulcers. Plast Aesthetic Res. 2014;1(2):65.
  43. Braund R, Hook S, Medlicott NJ. The role of topical growth factors in chronic wounds. Curr Drug Deliv. 2007;4(3):195–204.
  44. Lee DE, Ayoub N, Agrawal DK. Mesenchymal stem cells and cutaneous wound healing: novel methods to increase cell delivery and therapeutic efficacy. Stem Cell Res Ther. 2016;7(1):37.
  45. Vizoso F, Eiro N, Cid S, Schneider J, Perez-Fernandez R. Mesenchymal stem cell secretome: Toward cell-free therapeutic strategies in regenerative medicine. Int J Mol Sci. 2017;18(9):1852.
  46. Pawitan JA. Prospect of stem cell conditioned medium in regenerative medicine. Biomed Res Int. 2014;2014:1–14.
  47. Jeon YK, Jang YH, Yoo DR, Kim SN, Lee SK, Nam MJ. Mesenchymal stem cells’ interaction with skin: Wound-healing effect on fibroblast cells and skin tissue. Wound Repair Regen. 2010;18(6):655–61.
  48. Walter MNM, Wright KT, Fuller HR, MacNeil S, Johnson WEB. Mesenchymal stem cell-conditioned medium accelerates skin wound healing: An in vitro study of fibroblast and keratinocyte scratch assays. Exp Cell Res. 2010;316(7):1271–81.
  49. Ojeh NO, Navsaria HA. An in vitro skin model to study the effect of mesenchymal stem cells in wound healing and epidermal regeneration. J Biomed Mater Res Part A. 2014;102(8):2785–92.
  50. Nie C, Yang D, Xu J, Si Z, Jin X, Zhang J. Locally administered adipose-derived stem cells accelerate wound healing through differentiation and vasculogenesis. Cell Transplant. 2011 Mar;20(2):205–16.
  51. Lee SH, Jin SY, Song JS, Seo KK, Cho KH. Paracrine effects of adipose-derived stem cells on keratinocytes and dermal fibroblasts. Ann Dermatol. 2012;24(2):136.
  52. Ghieh F, Jurjus R, Ibrahim A, Geagea AG, Daouk H, El Baba B, et al. The use of stem cells in burn wound healing: A review. BioMed Research International. 2015;2015: 684084.
  53. Xu Y, Guo S, Wei C, Li H, Chen L, Yin C, et al. The comparison of adipose stem cell and placental stem cell in secretion characteristics and in facial antiaging. Stem Cells Int. 2016; 2016:7315830.
  54. 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 Oct 23;16(10):25476-501.
  55. Liu YL, Liu WH, Sun J, Hou TJ, Liu YM, Liu HR, et al. Mesenchymal stem cell-mediated suppression of hypertrophic scarring is p53 dependent in a rabbit ear model. Stem Cell Res Ther. 2014;5(6):136.
  56. Schrepfer S, Deuse T, Reichenspurner H, Fischbein MP, Robbins RC, Pelletier MP. Stem cell transplantation: The lung barrier. Transplant Proc. 2007;39(2):573–6.
  57. Comerota AJ, Link A, Douville J, Burchardt ER. Upper extremity ischemia treated with tissue repair cells from adult bone marrow. J Vasc Surg. 2010;52(3):723–9.
  58. Gholamrezanezhad A, Mirpour S, Bagheri M, Mohamadnejad M, Alimoghaddam K, Abdolahzadeh L, et al. In vivo tracking of 111In-oxine labeled mesenchymal stem cells following infusion in patients with advanced cirrhosis. Nucl Med Biol. 2011;38(7):961–7.
  59. Gupta PK, Chullikana A, Parakh R, Desai S, Das A, Gottipamula S, et al. A double blind randomized placebo controlled phase I/II study assessing the safety and efficacy of allogeneic bone marrow derived mesenchymal stem cell in critical limb ischemia. J Transl Med. 2013;11(1):143.
  60. Kim S-W, Han H, Chae G-T, Lee S-H, Bo S, Yoon J-H, et al. Successful stem cell therapy using umbilical cord blood-derived multipotent stem cells for Buerger’s Disease and ischemic limb disease animal model. Stem Cells. 2006;24(6):1620–6.

How to Cite

Tan, S. T., Firmansyah, Y., Halim, K. C., Aisyah, P. B. ., & Hendrawan, S. (2024). Effectiveness of conditioned medium mesenchymal stem cells intracutaneous for trophic ulcer due to morbun hansen. Bali Medical Journal, 13(1), 725–736.




Search Panel

Sukmawati Tansil Tan
Google Scholar
BMJ Journal

Yohanes Firmansyah
Google Scholar
BMJ Journal

Kelvin Cristian Halim
Google Scholar
BMJ Journal

Putri Bennya Aisyah
Google Scholar
BMJ Journal

Siufui Hendrawan
Google Scholar
BMJ Journal