Library - Ulcer and chronic wound healing

Organogenesis. 2015;11(4):183-206. doi: 10.1080/15476278.2015.1126018.

Mesenchymal stem cells: potential for therapy and treatment of chronic non-healing skin wounds.

Marfia G1Navone SE1Di Vito C2Ughi N3Tabano S4Miozzo M4Tremolada C5Bolla G6Crotti C3Ingegnoli F3Rampini P1Riboni L2Gualtierotti R3,Campanella R1.

Author information

1a Fondazione IRCCS Ca’Granda Ospedale Maggiore Policlinico; University of Milan; Neurosurgery Unit; Laboratory of Experimental Neurosurgery and Cell Therapy ; Milan , Italy.

2b University of Milan; Department of Medical Biotechnology and Translational Medicine; LITA-Segrate ; Milan , Italy.

3c Division of Rheumatology; Istituto Gaetano Pini; Milan Italy; Department of Clinical Science & Community Health; University of Milan ; Milan , Italy.

4d Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico; University of Milan; Division of Pathology ; Milan , Italy.

5e Istituto Image ; Milan , Italy.

6f Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico; University of Milan ; Milan , Italy.


Wound healing is a complex physiological process including overlapping phases (hemostatic/inflammatory, proliferating and remodeling phases). Every alteration in this mechanism might lead to pathological conditions of different medical relevance. Treatments for chronic non-healing woundsare expensive because reiterative treatments are needed. Regenerative medicine and in particular mesenchymal stem cells approach is emerging as new potential clinical application in wound healing. In the past decades, advance in the understanding of molecular mechanisms underlyingwound healing process has led to extensive topical administration of growth factors as part of wound care. Currently, no definitive treatment is available and the research on optimal wound care depends upon the efficacy and cost-benefit of emerging therapies. Here we provide an overview on the novel approaches through stem cell therapy to improve cutaneous wound healing, with a focus on diabetic wounds and Systemic Sclerosis-associated ulcers, which are particularly challenging. Current and future treatment approaches are discussed with an emphasis on recent advances.


adipose stem cells; autoimmune diseases; diabetes; mesenchymal stem cells; systemic sclerosis; ulcer; wound

Int J Low Extrem Wounds. 2012 Dec;11(4):244-53. doi: 10.1177/1534734612463935.

Mesenchymal stem cells/multipotent mesenchymal stromal cells (MSCs): potential role in healing cutaneouschronic wounds.

Zou JP1Huang SPeng YLiu HWCheng BFu XBXiang XF.

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1Guangzhou General Hospital of Guangzhou Command, GuangDong, The Key Laboratory of Trauma Treatment & Tissue Repair of Tropical Area, PLA, P R China.


Chronic wounds remain a major challenge in modern medicine and represent a significant health care burden. Several treatments have been suggested, but without a full understanding of the exact mechanism by which chronic wound occurs. Numerous studies have shown thatmesenchymal stem cells/multipotent mesenchymal stromal cells (MSCs) may have therapeutic potential in healing cutaneous chronic woundsthrough various mechanisms. So far, a series of hypotheses have been proposed, but a holistic image of them is lacking. This review provides a systematic analysis of recent research in animal models and preclinical or clinic trails to evaluate the potential role of MSCs in chronic cutaneouswound healing. Most important, we highlight how mesenchymal stem cells could potentially revolutionize our approach to treating cutaneouschronic wounds. Special attention should be focused on ongoing research regarding the challenges in using and prospects of MSCs in clinical settings.

Expert Opin Biol Ther. 2015;15(9):1285-92. doi: 10.1517/14712598.2015.1053867. Epub 2015 Jun 3.

Adipose-derived stem cells for wound repair and regeneration.

Shingyochi Y1Orbay HMizuno H.

Author information

1Juntendo University School of Medicine, Department of Plastic and Reconstructive Surgery , 2-1-1 Hongo Bunkyo-ku, Tokyo 1138421 , Japan.



The use of undifferentiated cells for cell-based tissue repair and regeneration strategies represents a promising approach for chronic wound healing. Multipotent adult stem cells isolated from adipose tissue, termed adipose-derived stem cells (ASCs), appear to be an ideal population of stem cells because they are autologous, non-immunogenic, plentiful, and easily obtained. Both preclinical and clinical studies have revealed that ASCs have potential for wound healing due to the mechanisms described below.


Both in vitro and in vivo studies demonstrated that ASCs not only differentiate into keratinocytes, fibroblasts, and endothelial cells, as evidenced by their morphology, expression of cell surface markers, and gene expression, but also secrete several soluble factors, which positively contribute to wound healing in a paracrine manner. Clinical trials have been conducted using autologous ASCs with great success.


There remain many concerns regarding the use of ASCs, including how these cells act as precursors of keratinocytes, fibroblasts, and endothelial cells, or as a secretion vehicle of soluble factors. Further studies are necessary to establish the optimal strategy for the treatment of chronic wounds in patients with different disease backgrounds.


adipose-derived stem cells; clinical trials; growth factors; regeneration; wound healing