Use of Stem Cells in Wound Healing
- 87 Downloads
Purpose of Review
This review provides an overview of the principal stages of wound healing, the populations of endogenous and therapeutic stem cells, applications of stem cells in specific types of wounds, and current approaches of stem cell delivery for tissue regeneration.
New uses of progenitor stem cells have been developed for the treatment of wounds. Stem cells improve wound healing through both local and paracrine effects. Stem cell populations of therapeutic utility include embryonic stem cells, induced pluripotent stem cells, adult bone marrow and adipose-derived mesenchymal stem cells, as well as stem cells from skin, cord blood, and extra fetal tissue. Induced pluripotent stem cells mitigate many of the ethical and immunogenic concerns related to use of embryonically derived stem cells.
Skin, the largest organ in the human body, serves as a protective barrier for mammals. Both aging and disease contribute to loss of skin barrier function, which can result in consequences such as chronic wounds. Recent advances in many types of stem cell therapy may revolutionize treatment of difficult wounds. Optimal techniques for obtaining and delivering stem cells are still being refined.
KeywordsStem cells Wound healing Chronic wounds Biologic therapies
Compliance with Ethical Standards
Conflict of Interest
The authors declare that they have no conflict of interest.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
Papers of particular interest, published recently, have been highlighted as: • Of importance
- 4.Chen M, Przyborowski M, Berthiaume F. Stem cells for skin tissue engineering and wound healing. Crit Rev Biomed Eng. 2009;37(4–5):399–421. https://doi.org/10.1615/critrevbiomedeng.v37.i4-5.50.CrossRefPubMedPubMedCentralGoogle Scholar
- 5.McGrath JA, Eady RAJ, Pope FM. Anatomy and organization of human skin. In: Burns T, Breathnach S, Cox N, Griffiths C, editors. Rook’s textbook of dermatology. 7th ed. Hoboken: Blackwell Publishing; 2004. p. 4190. https://doi.org/10.1002/9780470750520.ch3. ISBN 978-0-632-06429-8. Retrieved 2010-06-01.CrossRefGoogle Scholar
- 14.Bergen TV, Velde SVD, Vandewalle E, Moons L, Stalmans I. Improving patient outcomes following glaucoma surgery: state of the art and future perspectives. Clin Ophthalmol. 2014:857. https://doi.org/10.2147/opth.s48745.
- 15.Beitz JM. Pharmacologic impact (aka “breaking bad”) of medications on wound healing and wound development: a literature-based overview. Advances in pediatrics. https://www.ncbi.nlm.nih.gov/pubmed/28355136. Published March 2017. Accessed 6 June 2018.
- 20.Kumar A, Mohanty S, Gupta S, Paulkhurana SM. Stem cells of the hair follicular tissue: application in cell based therapy for vitiligo. Hair Ther Transplant. 2015;05(01). https://doi.org/10.4172/2167-0951.1000132.
- 32.• Denu RA, Nemcek S, Bloom DD, et al. Fibroblasts and mesenchymal stromal/stem cells are phenotypically indistinguishable. Acta Haematol. 2016;136(2):85–97. https://doi.org/10.1159/000445096 This study demonstrates indistinguishable cell surface makers and morphology between fibroblasts and mesenchymal stem cells. This supports our understanding that MSCs parallel fibroblasts in their wound healing capacity: both cell types secrete extracellular matrix and suppress the inflammatory cascade. CrossRefPubMedPubMedCentralGoogle Scholar
- 38.Jones EA, English A, Henshaw K, Kinsey SE, Markham AF, Emery P, et al. Enumeration and phenotypic characterization of synovial fluid multipotential mesenchymal progenitor cells in inflammatory and degenerative arthritis. Arthritis Rheum. 2004;50(3):817–27. https://doi.org/10.1002/art.20203.CrossRefPubMedGoogle Scholar
- 40.Frenette PS, Pinho S, Lucas D, Scheiermann C. Mesenchymal stem cell: keystone of the hematopoietic stem cell niche and a stepping-stone for regenerative medicine. Annu Rev Immunol. 2013;31(1):285–316. https://doi.org/10.1146/annurev-immunol-032712-095919.CrossRefPubMedGoogle Scholar
- 44.• Summa PGD, Schiraldi L, Cherubino M, et al. Adipose derived stem cells reduce fibrosis and promote nerve regeneration in rats. The Anatomical Record. 2018. https://doi.org/10.1002/ar.23841 This study illustrates the therapeutic potential of adipose derived stem cells by demonstrating reduced scar formation and increased nerve regeneration. CrossRefGoogle Scholar
- 47.Alexaki V-I, Simantiraki D, Panayiotopoulou M, Rasouli O, Venihaki M, Castana O, et al. Adipose tissue-derived mesenchymal cells support skin reepithelialization through secretion of KGF-1 and PDGF-BB: comparison with dermal fibroblasts. Cell Transplant. 2012;21(11):2441–54. https://doi.org/10.3727/096368912x637064.CrossRefPubMedGoogle Scholar
- 57.Sebastiano V, Zhen HH, Haddad B, Bashkirova E, Melo SP, Wang P, et al. Human COL7A1-corrected induced pluripotent stem cells for the treatment of recessive dystrophic epidermolysis bullosa. Sci Transl Med. 2014;6(264):264ra163. https://doi.org/10.1126/scitranslmed.3009540.CrossRefPubMedPubMedCentralGoogle Scholar
- 66.Németh K, Leelahavanichkul A, Yuen PST, Mayer B, Parmelee A, Doi K, et al. Bone marrow stromal cells attenuate sepsis via prostaglandin E2-dependent reprogramming of host macrophages to increase their interleukin-10 production. Nat Med. 2008;15(1):42–9. https://doi.org/10.1038/nm.1905.CrossRefPubMedPubMedCentralGoogle Scholar
- 67.Benbernou N, Esnault S, Shin HCK, Fekkar H, Guenounou M. Differential regulation of IFN-gamma, IL-10 and inducible nitric oxide synthase in human T cells by cyclic AMP-dependent signal transduction pathway. Immunology. 1997;91(3):361–8. https://doi.org/10.1046/j.1365-2567.1997.00260.x.CrossRefPubMedPubMedCentralGoogle Scholar
- 70.Yang Y, Zhang W, Li Y, Fang G, Zhang K. Scalded skin of rat treated by using fibrin glue combined with allogeneic bone marrow mesenchymal.Google Scholar
- 72.Basu S, Ali H, Sangwan VS. Clinical outcomes of repeat autologous cultivated limbal epithelial transplantation for ocular surface burns. Am J Ophthalmol. 2012;153(4). https://doi.org/10.1016/j.ajo.2011.09.016.40.
- 77.Cohn Yakubovich D, Sheyn D, Bez M, Schary Y, Yalon E, Sirhan A, et al. Systemic administration of mesenchymal stem cells combined with parathyroid hormone therapy synergistically regenerates multiple rib fractures. Stem Cell Res Ther. 2017;8:51. https://doi.org/10.1186/s13287-017-0502-9.CrossRefPubMedPubMedCentralGoogle Scholar
- 79.Rustad KC, Wong VW, Sorkin M, Glotzbach JP, Major MR, Rajadas J, et al. Enhancement of mesenchymal stem cell angiogenic capacity and stemness by a biomimetic hydrogel scaffold. Biomaterials. 2012;33(1):80–90. https://doi.org/10.1016/j.biomaterials.2011.09.041.CrossRefPubMedGoogle Scholar
- 80.Stem cell basics. Sigma-Aldrich. https://www.sigmaaldrich.com/technical-documents/articles/biology/what-are-stem-cells.html. Accessed 5 June 2018.
- 81.Little M-T, Storb R. History of haematopoietic stem-cell transplantation. Nature News. https://www.nature.com/articles/nrc748. Published March 1, 2002. Accessed 5 June 2018.
- 82.Markers & methods to verify mesenchymal stem cell identity, potency, & quality. R&D Systems. https://www.rndsystems.com/resources/articles/markers-and-methods-verify-mesenchymal-stem-cell-identity-potency-and-quality. Accessed 5 June 2018.
- 83.Boston Children's Hospital. Boston Children’s Hospital. http://stemcell.childrenshospital.org/about-stem-cells/history/. Accessed 5 June 2018.
- 86.Wheeland RG. The technique and current status of pinch grafting. J Dermatol Surg Oncol. 1987;13(8):873–81. https://doi.org/10.1111/j.1524-4725.1987.tb00564.x.CrossRefPubMedGoogle Scholar
- 87.• Osborne SN, Schmidt MA, Harper JR. An automated and minimally invasive tool for generating autologous viable epidermal micrografts. Adv Skin Wound Care. 2016;29(2):57–64. https://doi.org/10.1097/01.ASW.0000476072.88818.aa This study outlines a novel, minimally invasive epidermal harvesting tool that aids in rapid wound healing and reduced scarring at both donor and recipient graft sites. CrossRefPubMedPubMedCentralGoogle Scholar