Stem Cell Based Soft Tissue Reconstruction

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DESCRIPTION (provided by applicant): Soft tissue defects cause physical and psychosocial suffering to patients. Cancer resection surgeries of breast and facial malignancies lead to disfiguration. Injuries during war or accidents result in soft tissue wounds and defects. For decades, surgeons have utilized their creative wisdom to improve soft tissue reconstruction procedures. However, current materials and/or approaches for soft tissue reconstruction suffer from intrinsic deficiencies largely beyond the surgeon's control. Autologous (patient's own) soft tissue grafts often are the clinical gold standard, but necessitate donor site morbidity. Foreign materials for soft tissue reconstruction have witnessed various levels of clinical success, but can fail unpredictably and with severe clinical consequences as exemplified by the reported negative sequela of silicone breast implants. The surgical literature is replete with continuing aspiration to 'grow' patient's own soft tissue grafts from stem cells for reconstruction needs. Despite a small number of isolated meritorious attempts to engineer soft tissue by cell-based approaches, the effort level on soft tissue engineering lags far behind hard (bone) tissue engineering. Our preliminary data demonstrate that human mesenchymal stem cells (hMSCs) encapsulated in a biocompatible hydrogel were capable of generating adipose tissue, verified by oil- red O staining and the expression of adipogenic mRNA, PPAR-?2. The maintenance of the shape and dimensions of the engineered adipose tissue, as a clinical need specified by our plastic surgeon collaborators, were nearly 100% after 4-week in vivo subcutaneous implantation of hMSC-derived soft tissue grafts in immunodeficient mice. The overall goal of this proposal is to optimize key parameters of the engineered soft tissue grafts toward our long-term goal to develop engineered soft tissue grafts from the patient's own adult stem cells for surgical reconstruction of soft tissue defects. An interdisciplinary team of biomedical engineers, biologists, biomaterial scientists, imaging scientists and surgical consultants have been assembled to meet the challenges of realizing our goals.