Effective delivery of stem cells using an extracellular matrix patch results in increased cell survival and proliferation and reduced scarring in skin wound healing.

Wound healing is one of the most complex biological processes and occurs in all tissues and organs of the body. In humans, fibrotic tissue, or scar, hinders function and is aesthetically unappealing. Stem cell therapy offers a promising new technique for aiding in wound healing; however, current findings show that stem cells typically die and/or migrate from the wound site, greatly decreasing efficacy of the treatment. Here, we demonstrate effectiveness of a stem cell therapy for improving wound healing in the skin and reducing scarring by introducing stem cells using a natural patch material. Adipose-derived stromal cells were introduced to excisional wounds created in mice using a nonimmunogenic extracellular matrix (ECM) patch material derived from porcine small-intestine submucosa (SIS). The SIS served as an attractive delivery vehicle because of its natural ECM components, including its collagen fiber network, providing the stem cells with a familiar structure. Experimental groups consisted of wounds with stem cell-seeded patches removed at different time points after wounding to determine an optimal treatment protocol. Stem cells delivered alone to skin wounds did not survive post-transplantation as evidenced by bioluminescence in vivo imaging. In contrast, delivery with the patch enabled a significant increase in stem cell proliferation and survival. Wound healing rates were moderately improved by treatment with stem cells on the patch; however, areas of fibrosis, indicating scarring, were significantly reduced in wounds treated with the stem cells on the patch compared to untreated wounds.

[1]  J. Molès,et al.  Potential of a PLA–PEO–PLA-Based Scaffold for Skin Tissue Engineering: In Vitro Evaluation , 2012, Journal of biomaterials science. Polymer edition.

[2]  K. Cho,et al.  Paracrine Effects of Adipose-Derived Stem Cells on Keratinocytes and Dermal Fibroblasts , 2012, Annals of dermatology.

[3]  Robert A. Brown,et al.  A rapid fabricated living dermal equivalent for skin tissue engineering: an in vivo evaluation in an acute wound model. , 2012, Tissue engineering. Part A.

[4]  Yilin Cao,et al.  Cryopreservation of tissue-engineered epithelial sheets in trehalose. , 2011, Biomaterials.

[5]  T. Couffinhal,et al.  Secreted Frizzled-Related Protein-1 Improves Postinfarction Scar Formation Through a Modulation of Inflammatory Response , 2011, Arteriosclerosis, thrombosis, and vascular biology.

[6]  Yan Jin,et al.  Synergistic angiogenesis promoting effects of extracellular matrix scaffolds and adipose-derived stem cells during wound repair. , 2011, Tissue engineering. Part A.

[7]  M. Longaker,et al.  Surgical Approaches to Create Murine Models of Human Wound Healing , 2010, Journal of biomedicine & biotechnology.

[8]  C. Jackson,et al.  The Fat-Fed Apolipoprotein E Knockout Mouse Brachiocephalic Artery in the Study of Atherosclerotic Plaque Rupture , 2010, Journal of biomedicine & biotechnology.

[9]  K. Kishi,et al.  Wound-associated skin fibrosis: mechanisms and treatments based on modulating the inflammatory response. , 2010, Endocrine, metabolic & immune disorders drug targets.

[10]  Pauline Chu,et al.  Imaging survival and function of transplanted cardiac resident stem cells. , 2009, Journal of the American College of Cardiology.

[11]  Jennifer T. Blundo,et al.  In vivo imaging and evaluation of different biomatrices for improvement of stem cell survival , 2007, Journal of tissue engineering and regenerative medicine.

[12]  R. Ritchie,et al.  Analysis of the material properties of early chondrogenic differentiated adipose-derived stromal cells (ASC) using an in vitro three-dimensional micromass culture system. , 2007, Biochemical and biophysical research communications.

[13]  Ahmad Y. Sheikh,et al.  Collagen Matrices Enhance Survival of Transplanted Cardiomyoblasts and Contribute to Functional Improvement of Ischemic Rat Hearts , 2006, Circulation.

[14]  Zuquan Ding,et al.  [Elastic modulus of small intestinal submucosa]. , 2006, Zhongguo xiu fu chong jian wai ke za zhi = Zhongguo xiufu chongjian waike zazhi = Chinese journal of reparative and reconstructive surgery.

[15]  G. Gurtner,et al.  Quantitative and reproducible murine model of excisional wound healing , 2004, Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society.

[16]  Ann E Rundell,et al.  Biaxial strength of multilaminated extracellular matrix scaffolds. , 2004, Biomaterials.

[17]  F A Auger,et al.  Mechanisms of wound reepithelialization: hints from a tissue‐engineered reconstructed skin to long‐standing questions , 2001, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[18]  D. Lukovic,et al.  Membrane-targeted green fluorescent protein reliably and uniquely marks cells through apoptotic death. , 2001, Cytometry.

[19]  S. Badylak,et al.  Identification of extractable growth factors from small intestinal submucosa , 1997, Journal of cellular biochemistry.

[20]  G. Bergamini,et al.  Ultrastructural and morphometrical evaluations on normal human dermal connective tissue – the influence of age, sex and body region , 1996, The British journal of dermatology.