Stem Cell Based Soft Tissue Reconstruction

描述(申请人提供)：软组织缺陷会给患者带来身体和心理上的痛苦。乳腺癌和面部恶性肿瘤的癌症切除手术会导致毁容。战争或事故中的伤害会导致软组织损伤和缺陷。几十年来，外科医生一直在利用他们的创造性智慧来改进软组织重建程序。然而，目前用于软组织重建的材料和/或方法存在着很大程度上超出外科医生控制的固有缺陷。自体(患者自己的)软组织移植通常是临床的黄金标准，但有必要使供区发生并发症。国外用于软组织重建的材料在临床上取得了不同程度的成功，但可能会出现不可预测的失败，并带来严重的临床后果，如报道的硅胶乳房植入物的负面后遗症。外科文献中充斥着从干细胞中‘培养’患者自己的软组织移植物以满足重建需求的持续抽吸。尽管通过基于细胞的方法对软组织工程进行了少量有价值的孤立尝试，但软组织工程的努力水平远远落后于硬(骨)组织工程。通过油红O染色和成脂基因PPAR-2的表达，我们的初步数据表明，包裹在生物相容性水凝胶中的人骨髓间充质干细胞(HMSCs)能够生成脂肪组织。2.将hMSC来源的软组织移植到免疫缺陷小鼠体内皮下4周后，工程化脂肪组织的形状和尺寸保持了近100%，这是我们整形外科医生的合作者指定的临床需要。这项建议的总体目标是优化工程化软组织移植物的关键参数，以实现我们的长期目标，即从患者自己的成人干细胞开发工程化软组织移植物，用于软组织缺损的外科重建。一支由生物医学工程师、生物学家、生物材料科学家、成像科学家和外科顾问组成的跨学科团队已经组建，以迎接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.