Vol 10, No 2 (2021)
Review article
Published online: 2020-12-01

open access

Page views 891
Article views/downloads 492
Get Citation

Connect on Social Media

Connect on Social Media

Strategies to increase the effectiveness of wound healing therapy with mesenchymal stem cells in diabetic patients

Maksymilian Gofron1, Beata Mrozikiewicz-Rakowska1, Damian Sieńko1, Leszek Czupryniak1
Clin Diabetol 2021;10(2):226-233.

Abstract

Administration of mesenchymal stem cells (MSC) into the wound seems a promising therapy in the management of hard-to-heal wounds in diabetic patients. We still do not have algorithms that would precisely define appropriate use of this therapy. However, the latest research results indicate multidirectional effects of MSC therapy (improvement of blood supply and tissue granulation within the wound, formation of superficial skin layers), as well as differences in the treatment efficacy between transplantation of cells obtained from a healthy person (allogeneic graft) and transplantation of cells obtained from the diabetic host (autologous graft). Various modifications of MSC therapy lead to more rapid wound healing, and this therapy may be a breakthrough in the treatment of chronic wounds in diabetic patients. In this article, we reviewed the up-to-date knowledge on the use of MSC in the treatment of hard-to-heal wounds in diabetes.

Article available in PDF format

View PDF Download PDF file

References

  1. Jeffcoate WJ, Price P, Harding KG, et al. International Working Group on Wound Healing and Treatments for People with Diabetic Foot Ulcers. Wound healing and treatments for people with diabetic foot ulcers. Diabetes Metab Res Rev. 2004; 20 Suppl 1: S78–S89.
  2. Akturk A, van Netten JJ, Scheer R, et al. Ulcer-free survival days and ulcer healing in patients with diabetic foot ulcers: A prospective cohort study. Int Wound J. 2019; 16(6): 1365–1372.
  3. Pound N, Chipchase S, Treece K, et al. Ulcer-free survival following management of foot ulcers in diabetes. Diabet Med. 2005; 22(10): 1306–1309.
  4. Ndosi M, Wright-Hughes A, Brown S, et al. Prognosis of the infected diabetic foot ulcer: a 12-month prospective observational study. Diabet Med. 2018; 35(1): 78–88.
  5. Hassan WUl, Greiser U, Wang W. Role of adipose-derived stem cells in wound healing. Wound Repair Regen. 2014; 22(3): 313–325.
  6. Fui L, Lok M, Govindasamy V, et al. Understanding the multifaceted mechanisms of diabetic wound healing and therapeutic application of stem cells conditioned medium in the healing process. Journal of Tissue Engineering and Regenerative Medicine. 2019; 13(12): 2218–2233.
  7. Kyung-Chul Moon, Hyun-Suk Suh, Ki-Bum Kim, Seung-Kyu Han, Ki-Won Young, Jin-Woo Lee, Mi-Hyung Kim. Potential of Allogeneic Adipose-Derived Stem Cell-Hydrogel Complex for Treating Diabetic Foot Ulcers. Epub. 2019.
  8. Tyeb S, Shiekh PA, Verma V, et al. Adipose-Derived Stem Cells (ADSCs) Loaded Gelatin-Sericin-Laminin Cryogels for Tissue Regeneration in Diabetic Wounds. Biomacromolecules. 2020; 21(2): 294–304.
  9. Wu YY, Jiao YP, Xiao LL, et al. Experimental Study on Effects of Adipose-Derived Stem Cell-Seeded Silk Fibroin Chitosan Film on Wound Healing of a Diabetic Rat Model. Ann Plast Surg. 2018; 80(5): 572–580.
  10. Edwards N, Feliers D, Zhao Q, et al. An electrochemically deposited collagen wound matrix combined with adipose-derived stem cells improves cutaneous wound healing in a mouse model of type 2 diabetes. J Biomater Appl. 2018; 33(4): 553–565.
  11. Kaisang L, Siyu W, Lijun F, et al. Adipose-derived stem cells seeded in Pluronic F-127 hydrogel promotes diabetic wound healing. J Surg Res. 2017; 217: 63–74.
  12. Joaquin Cortiella, Joan E Nichols, Koji Kojima, Lawrence J Bonassar, Phong Dargon, Amit K Roy, Martin P Vacant, Jean A Niles, Charles A Vacanti. Tissue-engineered Lung: An in Vivo and in Vitro Comparison of Polyglycolic Acid and Pluronic F-127 Hydrogel/Somatic Lung Progenitor Cell Constructs to Support Tissue Growth. Tissue Eng.
  13. Chen WJ, Huang JW, Niu CC, et al. Use of fluorescence labeled mesenchymal stem cells in pluronic F127 and porous hydroxyapatite as a bone substitute for posterolateral spinal fusion. J Orthop Res. 2009; 27(12): 1631–1636.
  14. Shi Q, Qian Z, Liu D, et al. GMSC-Derived exosomes combined with a chitosan/silk hydrogel sponge accelerates wound healing in a diabetic rat skin defect model. Front Physiol. 2017; 8: 904.
  15. Yuka Kato, Takanori Iwata, Shunichi Morikawa, Masayuki Yamato, Teruo Okano, Yasuko Uchigata. Allogeneic Transplantation of an Adipose-Derived Stem Cell Sheet Combined With Artificial Skin Accelerates Wound Healing in a Rat Wound Model of Type 2 Diabetes and Obesity. Diabetes. 2015.
  16. Seo E, Lim JS, Jun JB, et al. Exendin-4 in combination with adipose-derived stem cells promotes angiogenesis and improves diabetic wound healing. J Transl Med. 2017; 15(1): 35.
  17. Oses C, Olivares B, Ezquer M, et al. Preconditioning of adipose tissue-derived mesenchymal stem cells with deferoxamine increases the production of pro-angiogenic, neuroprotective and anti-inflammatory factors: Potential application in the treatment of diabetic neuropathy. PLoS One. 2017; 12(5): e0178011.
  18. Li Na, Yang YJ, Qian HY, et al. Intravenous administration of atorvastatin-pretreated mesenchymal stem cells improves cardiac performance after acute myocardial infarction: role of CXCR4. Am J Transl Res. 2015; 7(6): 1058–1070.
  19. Lafosse A, Dufeys C, Beauloye C, et al. Impact of hyperglycemia and low oxygen tension on adipose-derived stem cells compared with dermal fibroblasts and keratinocytes: importance for wound healing in type 2 diabetes. PLoS One. 2016; 11(12): e0168058.
  20. Tong C, Hao H, Xia L, et al. Hypoxia pretreatment of bone marrow-derived mesenchymal stem cells seeded in a collagen-chitosan sponge scaffold promotes skin wound healing in diabetic rats with hindlimb ischemia. Wound Repair Regen. 2016; 24(1): 45–56.
  21. Liu J, Hao H, Xia L, et al. Hypoxia pretreatment of bone marrow mesenchymal stem cells facilitates angiogenesis by improving the function of endothelial cells in diabetic rats with lower ischemia. PLoS One. 2015; 10(5): e0126715.
  22. Schive SW, Mirlashari MR, Hasvold G, et al. Human adipose-derived mesenchymal stem cells respond to short-term hypoxia by secreting factors beneficial for human islets in vitro and potentiate antidiabetic effect in vivo. Cell Med. 2017; 9(3): 103–116.
  23. Chen J, Chen J, Cheng Y, et al. Mesenchymal stem cell-derived exosomes protect beta cells against hypoxia-induced apoptosis via miR-21 by alleviating ER stress and inhibiting p38 MAPK phosphorylation. Stem Cell Res Ther. 2020; 11(1): 97.
  24. Mas-Bargues C, Sanz-Ros J, Román-Domínguez A, et al. Relevance of oxygen concentration in stem cell culture for regenerative medicine. Int J Mol Sci. 2019; 20(5).
  25. Lian K, Wang Q, Zhao S, et al. Pretreatment of diabetic adipose-derived stem cells with mitoTEMPO reverses their defective proangiogenic function in diabetic mice with critical limb ischemia. Cell Transplant. 2019; 28(12): 1652–1663.
  26. Peng Z, Yang X, Qin J, et al. Glyoxalase-1 overexpression reverses defective proangiogenic function of diabetic adipose-derived stem cells in streptozotocin-induced diabetic mice model of critical limb ischemia. Stem Cells Transl Med. 2017; 6(1): 261–271.