Stem Cell Based Soft Tissue Reconstruction

描述（由申请人提供）：软组织缺损会给患者带来生理和心理上的痛苦。乳房和面部恶性肿瘤的肿瘤切除手术导致毁容。在战争或事故中受伤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进软组织重建手术。然而，目前用于软组织重建的材料和/或方法在很大程度上存在外科医生无法控制的内在缺陷。自体（患者自身）软组织移植通常是临床金标准，但必然导致供体部位的发病率。用于软组织重建的外来材料在临床上取得了不同程度的成功，但也可能出现不可预测的失败，并带来严重的临床后果，硅胶乳房植入物的负面后遗症就是一个例子。外科文献中充满了持续的渴望，即从干细胞中“生长”患者自己的软组织移植物以满足重建需求。尽管有少数独立的有价值的尝试通过基于细胞的方法来设计软组织，但软组织工程的努力水平远远落后于硬（骨）组织工程。我们的初步数据表明，包裹在生物相容性水凝胶中的人间充质干细胞（hMSCs）能够生成脂肪组织，通过油红O染色和脂肪生成mRNA PPAR- 2的表达证实了这一点。作为我们的整形外科合作者指定的临床需要，在免疫缺陷小鼠体内皮下植入hmsc来源的软组织移植物4周后，工程脂肪组织的形状和尺寸的维持率接近100%。本方案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，即从患者自身的成体干细胞中开发工程化软组织移植物，用于软组织缺损的外科重建。一个由生物医学工程师、生物学家、生物材料科学家、成像科学家和外科顾问组成的跨学科团队已经聚集在一起，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.