Stem Cell Based Soft Tissue Reconstruction

描述（由申请方提供）：软组织缺损会给患者造成身体和心理痛苦。乳房及颜面部恶性肿瘤切除手术常导致毁容。在战争或事故中受伤会导致软组织损伤和缺陷。几十年来，外科医生利用他们的创造性智慧来改善软组织重建手术。然而，目前用于软组织重建的材料和/或方法存在内在缺陷，这在很大程度上超出了外科医生的控制。自体（患者自身）软组织移植通常是临床的金标准，但需要供区发病率。用于软组织重建的异物已经取得了不同程度的临床成功，但可能会不可预测地失败，并产生严重的临床后果，如报告的硅胶乳房植入体的不良后遗症所示。外科文献充满了持续的愿望，从干细胞中“生长”患者自己的软组织移植物以满足重建需求。尽管有少数孤立的有价值的尝试工程软组织的细胞为基础的方法，努力水平软组织工程远远落后于硬（骨）组织工程。我们的初步数据表明，人骨髓间充质干细胞（hMSCs）封装在生物相容性水凝胶能够产生脂肪组织，油红O染色和成脂mRNA，过氧化物酶体增殖物激活受体-？2.在免疫缺陷小鼠体内皮下植入hMSC衍生的软组织移植物4周后，作为我们的整形外科医生合作者指定的临床需求，工程化脂肪组织的形状和尺寸的维持接近100%。该提案的总体目标是优化工程软组织移植物的关键参数，以实现我们的长期目标，即从患者自身的成体干细胞开发工程软组织移植物，用于软组织缺损的手术重建。一个由生物医学工程师、生物学家、生物材料科学家、成像科学家和手术顾问组成的跨学科团队已经组建起来，以应对实现我们目标的挑战。

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.