Swathi Balaji1, Sundeep G Keswani1, Timothy M Crombleholme2. 1. Division of Pediatric, General, Thoracic and Fetal Surgery, Center for Molecular Fetal Therapy, Cincinnati Children's Hospital, The University of Cincinnati , Cincinnati, Ohio. ; College of Medicine, The University of Cincinnati , Cincinnati, Ohio. 2. Division of Pediatric, General, Thoracic and Fetal Surgery, Center for Molecular Fetal Therapy, Cincinnati Children's Hospital, The University of Cincinnati , Cincinnati, Ohio. ; College of Medicine, The University of Cincinnati , Cincinnati, Ohio. ; Center for Children's Surgery, Division of General, Thoracic, and Fetal Surgery, Children's Hospital Colorado, The University of Colorado School of Medicine , Aurora, Colorado. ; The University of Colorado School of Medicine , Aurora, Colorado.
Abstract
BACKGROUND: Mesenchymal stem cells (MSCs) are key to regenerative wound healing. MSCs have spatial memory and respond to local environment. MSCs orchestrate wound repair by: (1) structural repair via cellular differentiation; (2) immune-modulation; (3) secretion of growth factors that drive neovascularization and re-epithelialization; and (4) mobilization of resident stem cells. THE PROBLEM: Autologous bone-marrow-derived cells and MSCs demonstrate improved healing and tissue-integrity in animal models and clinical trials. However, the effects are variable and the mechanisms of MSC-mediated wound healing are not fully understood. The mammalian MSC niche and signaling sequences and factors affecting their homing, differentiation, viability, and safety need to be characterized to get full benefits of MSC cellular therapy. BASIC/CLINICAL SCIENCE ADVANCES: MSCs can be isolated from bone-marrow, and less-invasive tissues such as adipose, gingiva, muscle, and umbilical cord, with similar functional effects. However, isolation, culture conditions, and markers used to identify and trace the lineage of these MSCs have not been standardized, which is crucial to determine the extent to which MSCs act as multipotent stem cells or sources of secreted factors in wounds. CLINICAL CARE RELEVANCE: In chronic nonhealing wounds, where efficacy of conventional therapies is unsatisfactory, autotransplantation of MSCs could accelerate wound healing, promote regeneration and restoration of tissue integrity, and reduce recurrence of wounds at characteristically predisposed sites. CONCLUSION: Regenerative medicine and novel wound therapies using autologous stem cells holds great promise for clinical management of difficult wounds. The ideal candidate stem cells can be used to repopulate the wound bed to mediate appropriate epidermal and dermal regeneration and promote efficient wound repair, while modulating the immune system to prevent infection.
BACKGROUND: Mesenchymal stem cells (MSCs) are key to regenerative wound healing. MSCs have spatial memory and respond to local environment. MSCs orchestrate wound repair by: (1) structural repair via cellular differentiation; (2) immune-modulation; (3) secretion of growth factors that drive neovascularization and re-epithelialization; and (4) mobilization of resident stem cells. THE PROBLEM: Autologous bone-marrow-derived cells and MSCs demonstrate improved healing and tissue-integrity in animal models and clinical trials. However, the effects are variable and the mechanisms of MSC-mediated wound healing are not fully understood. The mammalian MSC niche and signaling sequences and factors affecting their homing, differentiation, viability, and safety need to be characterized to get full benefits of MSC cellular therapy. BASIC/CLINICAL SCIENCE ADVANCES: MSCs can be isolated from bone-marrow, and less-invasive tissues such as adipose, gingiva, muscle, and umbilical cord, with similar functional effects. However, isolation, culture conditions, and markers used to identify and trace the lineage of these MSCs have not been standardized, which is crucial to determine the extent to which MSCs act as multipotent stem cells or sources of secreted factors in wounds. CLINICAL CARE RELEVANCE: In chronic nonhealing wounds, where efficacy of conventional therapies is unsatisfactory, autotransplantation of MSCs could accelerate wound healing, promote regeneration and restoration of tissue integrity, and reduce recurrence of wounds at characteristically predisposed sites. CONCLUSION: Regenerative medicine and novel wound therapies using autologous stem cells holds great promise for clinical management of difficult wounds. The ideal candidate stem cells can be used to repopulate the wound bed to mediate appropriate epidermal and dermal regeneration and promote efficient wound repair, while modulating the immune system to prevent infection.
Authors: Ashley Gordon; Elliott D Kozin; Sundeep G Keswani; Sachin S Vaikunth; Anna B Katz; Philip W Zoltick; Michele Favata; Antoneta P Radu; Louis J Soslowsky; Meenhard Herlyn; Timothy M Crombleholme Journal: Wound Repair Regen Date: 2007-12-13 Impact factor: 3.617
Authors: Marija Mazor; Annabelle Cesaro; Mazen Ali; Thomas M Best; Eric Lespessaille; Hechmi Toumi Journal: Int J Mol Sci Date: 2017-08-12 Impact factor: 5.923