Dr. Susan Volk has previous basic science training in an NIH-sponsored VMD-PhD program and subsequently completed subspecialty clinical training as a veterinary surgeon. This proposal involves a new research direction for her, focusing on mesenchymal stem cell (MSC) based therapy for chronic cutaneous wounds and the molecular mechanisms of wound healing. The mentor, Dr. Alan Flake, will contribute expertise in the field of stem cell therapies and guide the candidate in developing an independent research program. Additional contributors will provide expertise in the fields of wound healing, dermatopathology and extracellular matrix biology. The academic component will include seminars, training in research ethics, and graduate-level courses. The candidate's limited clinical activities as a small animal soft tissue surgeon will complement her basic science investigation. Research will focus on establishing vulnerary efficacy of topically applied MSC to treat ischemic wounds and dissecting mechanisms of their therapeutic effects. Ischemic wounds create a formidable clinical challenge, with prolonged hospitalization and substantial healthcare expenditure. To date, effective therapies for ischemic ulcers and other chronic nonhealing wounds are lacking. Evidence in this proposal suggests that bone marrow derived MSC improve healing of ischemic wounds. The hypothesis to be tested is that MSC improve ischemic wound healing by both direct and indirect mechanisms.
Aim1 will evaluate the capacity of MSC to significantly improve the rate at which ischemic wounds heal by promoting contraction, epithelialization and granulation tissue formation. This will be accomplished using two models of ischemic wound healing: an established rabbit ear model and a murine model that will be characterized.
Aim 2 will test the hypotheses that MSC contribute directly to the wound healing as a myofibroblast and indirectly by producing paracrine factors that promote angiogenesis and epithelialization. It is anticipated that these studies may lead to tissue engineering approaches for treating ischemic wounds;using ex vivo expanded MSC and also provide substantial new insights into molecular mechanisms that are critical for healing ischemic tissues. This combination of training and research will allow the candidate to transition to a fully independent research investigator making contributions to the field of soft-tissue repair, while also retaining ties to the clinical veterinary community.
|Rak, Gregory D; Osborne, Lisa C; Siracusa, Mark C et al. (2016) IL-33-Dependent Group 2 Innate Lymphoid Cells Promote Cutaneous Wound Healing. J Invest Dermatol 136:487-496|
|Brisson, Becky K; Mauldin, Elizabeth A; Lei, Weiwei et al. (2015) Type III Collagen Directs Stromal Organization and Limits Metastasis in a Murine Model of Breast Cancer. Am J Pathol 185:1471-86|
|Rak, Gregory D; Osborne, Lisa C; Siracusa, Mark C et al. (2015) IL-33-Dependent Group 2 Innate Lymphoid Cells Promote Cutaneous Wound Healing. J Invest Dermatol :|
|Miedel, Emily L; Brisson, Becky K; Hamilton, Todd et al. (2015) Type III collagen modulates fracture callus bone formation and early remodeling. J Orthop Res 33:675-84|
|Volk, Susan W; Shah, Shalin R; Cohen, Arthur J et al. (2014) Type III collagen regulates osteoblastogenesis and the quantity of trabecular bone. Calcif Tissue Int 94:621-31|
|Volk, Susan W; Bohling, Mark W (2013) Comparative wound healing--are the small animal veterinarian's clinical patients an improved translational model for human wound healing research? Wound Repair Regen 21:372-81|
|Volk, Susan W; Theoret, Christine (2013) Translating stem cell therapies: the role of companion animals in regenerative medicine. Wound Repair Regen 21:382-94|
|Volk, Susan W; Wang, Yanjian; Hankenson, Kurt D (2012) Effects of donor characteristics and ex vivo expansion on canine mesenchymal stem cell properties: implications for MSC-based therapies. Cell Transplant 21:2189-200|
|Volk, Susan W; Wang, Yanjian; Mauldin, Elizabeth A et al. (2011) Diminished type III collagen promotes myofibroblast differentiation and increases scar deposition in cutaneous wound healing. Cells Tissues Organs 194:25-37|