Stem Cells Therapy as Anti-scar Treatment

Scars are a consequence of cutaneous wound healing that can be both unsightly and detrimental to the function of the tissue. Scar tissue is generated by excessive deposition of extracellular matrix tissue by wound healing fibroblasts and myofibroblasts. Hypertrophic scars generally occur after injury to the deep layers of the dermis. Scarring is not a necessary process to repair the dermal tissues. Rather, scar tissue forms due to specific mechanisms that occur during the adult wound healing process and are modulated primarily by the inflammatory response at the site of injury.

Excessive scarring (Hypertrophic Scars or Keloid), first described in the Smith papyrus about 1700 BC, it may occur after any type of injury including burns, lacerations, abrasions, piercings, surgical incisions, or injections. Excessive scars like hypertrophic scars or keloids are scars that present with an excess of dermal collagen, rising above skin level. Such lesions not only are cosmetically unattractive, but may also limit joint function and cause uncomfortable symptoms such as pain and pruritis. The resulting psychological burden affects the patient’s quality of life and escalates health care costs. Although the definitive process underlying such scar formation is yet to be elucidated, the upregulated, exaggerated inflammatory response has been found to be a critical step in achieving excessive scars.

 Scars are characterized by a different appearance to the surrounding skin: discoloration, stiffness and roughness are features of scarring.

Lipofilling or lipotransfer is a novel and promising treatment method for reduction or prevention of dermal scars after injury. Studies shows evidence supports the scar reducing properties of adipose tissue grafts. However, the underlying mechanism by which lipofilling improves scar aspect and reduces neuropathic scar pain remains largely undiscovered.

Adipose-derived stem cells (ADSCs) are often described to be responsible for this therapeutic effect of lipofilling. The anti-scarring function of MSCs is related to the inhibition of both myofibroblast differentiation and NO production. The clinical efficacy of lipofilling in scar areas is determined by improvement of the appearance of a scar, such as size, thickness, stiffness, discoloration of the scar. In the case of painful scars, this effect can also be measured by a decrease in pain.  Efficacy of lipofilling as a means for pain reduction was investigated, most but not all studies reported a significant reduction of pain after treatment of painful scars.

The most pioneering clinical work for this procedure is taking place in Japan, by using cultured ADSCs (stem cells taking it from your body fat and send to specialised lab for incubation and multiplying it to a sufficient numbers for the treatment area) to inject underneath the scar area and this technique is not only good for treatment of wound scar but, also acne scars and for filling in frown lines and wrinkles.

The efficacy of lipofilling to improve scar appearance has been investigated in multiple studies and all some degree of amelioration in scar appearance after lipofilling & that mean the scars became less different from normal skin and/or became less visible, also most studies has reported that risks of lipofilling in scar areas are rather low or even none. 

Mesenchymal Stem Cells can increase the wound healing process and inhibit hyperplastic scar formation by down-regulation of TGF-β1, collagen type I and III. Mesenchymal stem cells derived from Adipose Tissue (ADSCs) preferable for this usage compared to mesenchymal stem cells derived from bone marrow BmSCs, as the relatively easy harvesting of a large amounts of adipose tissue, less pain during harvesting, and the multi-lineage capacity of differentiating into several cell types.

Chen et al. (2016) observed that ADSCs made the hyperplastic scars  smaller, flatter, and softer in comparison to control group in his study. A similar finding in Dososaputro et al (2017) study. 

Microscopically, scars display a loss of rete ridges, sebaceous glands and hair follicles. Also, they are characterized by increased dermal and epidermal thickness. The epidermal thickening is caused by excessive proliferation of keratinocytes. In the dermis, the thickening is caused by excessive extracellular matrix (ECM) production by myofibroblasts, mainly consisting of collagen type I, not only there is an increase in the amount of collagens, but also in the collagen fibre thickness, maturation and degree of disorganization. However, if myofibroblasts persist, scarring will be the end result. Adipocyte-Derived Stem Cells ADSCs significantly decreased collagen expression and deposition, and inhibited the trans-differentiation of fibroblasts, also, can inhibit the myofibroblast so, the proliferation, production and contraction of these fibroblasts were reduced, which indicates that growth factors and cytokines of ADSC have the ability to prevent or even to reverse dermal scarring.

Read More- References 

  1. Abdulrazzak,D.Moschidou, G. Jones, and P.V.Guillot, “Biological characteristics of stem cells from foetal, cord blood and extraembryonic tissues,” Journal of the Royal Society Interface, vol. 7, supplement 6, pp. S689–S706, 2010.
  2. Berman and H. C. Bieley, “Keloids,” Journal of the American Academy of Dermatology, vol. 33, no. 1, pp. 117–123, 1995.
  3. Bommie Florence Seo and Sung-No Jung,The Immunomodulatory Effects of Mesenchymal Stem Cells in Prevention or Treatment of Excessive Scars a Hindawi Publishing Corporation Stem Cells International Volume 2016, Article ID 6937976, 8 pages
  4. Bruno A, Delli Santi G, Fasciani L, Cempanari M, Palombo M, Palombo P. 2013; Burn scar lipofilling: immunohisto-chemical and clinical outcomes. J Craniofac Surg 24(5):1806–1814.
  5. C. Gurtner, S. Werner, Y. Barrandon, and M. T. Longaker, “Wound repair and regeneration,” Nature, vol. 453, no. 7193, pp. 314–321, 2008.
  6. Domergue, S., Bony, C., Maumus, M., Toupet, K., Frouin, E., Rigau, V., . . . Noel, D. (2016). Comparison between Stromal Vascular Fraction and Adipose Mesenchymal Stem Cells in Remodeling Hypertrophic Scars. PLoS One, 11(5), e0156161. doi: 10.1371/journal.pone.0156161
  7. Dominici, K. Le Blanc, I. Mueller et al., “Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement,” Cytotherapy, vol. 8, no. 4, pp. 315–317, 2006.
  8. Ehrlich HP, Desmouliere A, Diegelmann RF et al. 1994; Morphological and immunochemical differences between keloid and hypertrophic scar. Am J Pathol 145(1): 105–113.
  9. Fan, R. R. Varshney, L. Ren, D. Cai, and D.-A. Wang, “Synovium-derived mesenchymal stem cells: a new cell source for musculoskeletal regeneration,” Tissue Engineering B: Reviews, vol. 15, no. 1, pp. 75–86, 2009.
  10. F. Hamrahi, J. Goverman, W. Jung et al., “In vivo molecular imaging of murine embryonic stem cells delivered to a burn wound surface via Integra scaffolding,” Journal of Burn Care and Research, vol. 33, no. 2, pp. e49–e54, 2012.
  11. G. Gauglitz, H. C. Korting, T. Pavicic, T. Ruzicka, and M. G. Jeschke, “Hypertrophic scarring and keloids: pathomechanisms and current and emerging treatment strategies,” Molecular Medicine, vol. 17, no. 1-2, pp. 113–124, 2011.
  12. G. Walmsley, Z.N.Maan, V. W. Wong et al., “Scarless wound healing: chasing the holy grail,” Plastic and Reconstructive Surgery, vol. 135, no. 3, pp. 907–917, 2015.
  13. Huang SH, Wu SH, Chang KP et al. 2015a; Alleviation of neuropathic scar pain using autologous fat grafting. Ann Plast Surg 74 Suppl 2: S99–S104.
  14. I. Shumakov, N. A. Onishchenko, M. F. Rasulov, M. E. Krasheninnikov, and V. A. Zaidenov, “Mesenchymal bone marrow stem cells more effectively stimulate regeneration of deep burn wounds than embryonic fibroblasts,” Bulletin of Experimental Biology and Medicine, vol. 136, no. 2, pp. 192–195, 2003.
  15. J. Placik and V. L. Lewis Jr., “Immunologic associations of keloids,” Surgery, Gynecology & Obstetrics, vol. 175, no. 2, pp. 185–193, 1992.
  16.  Jackson, W. M., , L. J. N., & Tuan, a. R. S. (2012). . Stem Cell Research & Therapy
  17. J. Friedenstein, U. F. Deriglasova, N. N. Kulagina et al., “Precursors for fibroblasts in different populations of hematopoietic cells as detected by the in vitro colony assay method,” Experimental Hematology, vol. 2, no. 2, pp. 83–92, 1974.
  18. J. Sandel, “Embryo ethics—the moral logic of stem-cell research,” The New England Journal of Medicine, vol. 351, no. 3, pp. 207–209, 2004.
  19. Janjanin, F. Djouad, R.M. Shanti et al., “Human palatine tonsil: a new potential tissue source of multipotent mesenchymal progenitor cells,” Arthritis Research and Therapy, vol. 10, no. 4, article R83, 2008.
  20. Jazedje, P. M. Perin, C. E. Czeresnia et al., “Human fallopian tube: a new source of multipotent adult mesenchymal stem cells discarded in surgical procedures,” Journal of Translational Medicine, vol. 7, article 46, 2009.
  21. K. Kim, B. F. Seo, K. J. Kim, S. Lee, Y. H. Ryu, and J.W. Rhie, “Secretory factors of human chorion-derived stemcells enhance activation of human fibroblasts,” Cytotherapy, vol. 17, no. 3, pp. 301–309, 2015.
  22. K. Sen, G. M. Gordillo, S. Roy et al., “Human skin wounds: a major and snowballing threat to public health and the economy,” Wound Repair and Regeneration, vol. 17, no. 6, pp. 763–771, 2009.
  23. K. Kuo and R. S. Tuan, “Tissue engineering with mesenchymal stem cells,” IEEE Engineering in Medicine and Biology Magazine, vol. 22, no. 5, pp. 51–56, 2003.
  24. Klinger M, Caviggioli F, Klinger FM et al. 2013; Autologous fat graft in scar treatment. J Craniofac Surg 24(5):1610–1615.
  25. Klinger M, Marazzi M, Vigo D, Torre M. 2008; Fat injection for cases of severe burn outcomes: a new perspective of scar remodeling and reduction. Aesthetic Plast Surg 32(3): 465–469.
  26. M.Gimble and F.Guilak, “Differentiation potential of adipose derived adult stem (ADAS) cells,” Current Topics in Developmental Biology, vol. 58, pp. 137–160, 2003.
  27. Marshall CD, Hu MS, Leavitt T, Barnes LA, Lorenz HP, Longaker MT. Cutaneous Scarring: Basic Science, Current Treatments, and Future Directions. Advances in Wound Care. 2018;7(2):29-45. doi:10.1089/wound.2016.0696.
  28. Nie, D. Yang, J. Xu, Z. Si, X. Jin, and J. Zhang, “Locally administered adipose-derived stem cells accelerate wound healing through differentiation and vasculogenesis,” Cell Transplantation, vol. 20, no. 2, pp. 205–216, 2011.
  29. Panettiere P, Marchetti L, Accorsi D. 2009; The serial free fat transfer in irradiated prosthetic breast reconstructions. Aesthetic Plast Surg 33(5): 695–700.
  30. Ribuffo D, Atzeni M, Guerra M et al. 2013; Treatment of irradiated expanders: protective lipofilling allows immediate prosthetic breast reconstruction in the setting of postoperative radiotherapy. Aesthetic Plast Surg 37(6):1146–1152.
  31. Rigotti G, Marchi A, Galie M et al. 2007; Clinical treatment of radiotherapy tissue damage by lipoaspirate transplant: a healing process mediated by adipose-derived adul stem cells. Plast Reconstr Surg 119(5): 1409–1422; discussion 1423–1404.
  32. R. V. Shih, T. K. Kuo, A.-H. Yang, O. K. Lee, and C.-H. Lee, “Isolation and characterization of stem cells from the human parathyroid gland,” Cell Proliferation, vol. 42,no. 4, pp. 461–470, 2009.
  33. S. Choi, S.-E. Noh, S.-M. Lim et al., “Multipotency and growth characteristic of periosteum-derived progenitor cells for chondrogenic, osteogenic, and adipogenic differentiation,” Biotechnology Letters, vol. 30, no. 4, pp. 593–601, 2008
  34. Spiekman, M., van Dongen, J. A., Willemsen, J. C., Hoppe, D. L., van der Lei, B., & Harmsen, M. C. (2017). The power of fat and its adipose-derived stromal cells: emerging concepts for fibrotic scar treatment. J Tissue Eng Regen Med, 11(11), 3220-3235. doi: 10.1002/term.2213
  35. Sabapathy, B. Sundaram, V. M. Sreelakshmi, P. Mankuzhy, and S. Kumar, “Human Wharton’s jelly mesenchymal stem cells plasticity augments scar-free skin wound healing with hair growth,” PLoS ONE, vol. 9, no. 4, Article ID e93726, 2014.
  36. Sabapathy, S. Ravi, V. Srivastava, A. Srivastava, and S. Kumar, “Long-term cultured human term placenta-derived mesenchymal stem cells of maternal origin displays plasticity,” Stem Cells International, vol. 2012, Article ID 174328, 11 pages, 2012.
  37. T.-J. Huang, W. Sonoyama, Y. Liu, H. Liu, S. Wang, and S. Shi, “The hidden treasure in apical papilla: the potential role in pulp/dentin regeneration and bioroot engineering,” Journal of Endodontics, vol. 34, no. 6, pp. 645–651, 2008.
  38. Ulrich D, Ulrich F, van Doorn L, Hovius S. 2012; Lipofilling of perineal and vaginal scars: a new method for improvement of pain after episiotomy and perineal laceration. Plast Reconstr Surg 129(3): 593e–594e.
  39. Wesley M Jackson1, , L. J. N., 3, & Tuan4, a. R. S. (2012). . Stem Cell Res Ther(2012, 3:20).
  40. Wesley M Jackson1, , L. J. N., 3, & Tuan4, a. R. S. (2012). . Stem Cell Res Ther.
  41. Y. Jo, H.-J. Lee, S.-Y. Kook et al., “Isolation and characterization of postnatal stem cells from human dental tissues,” Tissue Engineering, vol. 13, no. 4, pp. 767–773, 2007.

Related Topics

Request a Call Back


This document is designed to supply useful information but is not to be regarded as advice specific to any particular case. It does not replace the need for a thorough consultation and all prospective patients should seek the advice of a qualified physician

Dr. Sahar Al Kazzaz

Close Menu