Human Adipose-Derived Mesenchymal Stem Cells in Cell Therapy: Safety and Feasibility in Different "Hospital Exemption" Clinical Applications

Based on immunomodulatory, osteogenic, and pro-angiogenic properties of adipose-derived stem cells (ASCs), this study aims to assess the safety and efficacy of ASC-derived cell therapies for clinical indications. Two autologous ASC-derived products were proposed to 17 patients who had not experienced any success with conventional therapies: (1) a scaffold-free osteogenic three-dimensional graft for the treatment of bone non-union and (2) a biological dressing for dermal reconstruction of non-healing chronic wounds. Safety was studied using the quality control of the final product (genetic stability, microbiological/mycoplasma/endotoxin contamination) and the in vivo evaluation of adverse events after transplantation. Feasibility was assessed by the ability to reproducibly obtain the final ASC-based product with specific characteristics, the time necessary for graft manufacturing, the capacity to produce enough material to treat the lesion, the surgical handling of the graft, and the ability to manufacture the graft in line with hospital exemption regulations. For 16 patients (one patient did not undergo grafting because of spontaneous bone healing), in-process controls found no microbiological/mycoplasma/endotoxin contamination, no obvious deleterious genomic anomalies, and optimal ASC purity. Each type of graft was reproducibly obtained without significant delay for implantation and surgical handling was always according to the surgical procedure and the implantation site. No serious adverse events were noted for up to 54 months. We demonstrated that autologous ASC transplantation can be considered a safe and feasible therapy tool for extreme clinical indications of ASC properties and physiopathology of disease.基于脂肪来源干细胞（adipose-derived stem cells，ASCs）的免疫调节、成骨及促血管生成特性，本研究旨在评估ASC来源细胞疗法针对临床适应证的安全性与有效性。本研究针对17例经传统疗法治疗无效的患者，提供两种自体ASC来源产品：（1）用于治疗骨不连的无支架成骨三维移植物；（2）用于慢性难愈性创面皮肤重建的生物敷料。安全性通过终产品质量控制（遗传稳定性、微生物/支原体/内毒素污染检测）以及移植后不良事件的体内评价进行评估。可行性则通过以下维度综合评判：可重复获取具备特定特性的终级ASC源性产品的能力、移植物制备所需时长、制备足够治疗病变所需材料的能力、移植物的手术操作性，以及符合医院豁免法规的移植物制备流程。16例患者（1例因自发性骨愈合未接受移植物移植）的过程质控结果显示，未检出微生物/支原体/内毒素污染，无明显有害基因组异常，且ASC纯度达标。两类移植物均可重复制备，未出现移植相关显著延迟，手术操作始终符合对应手术流程与植入部位要求。随访时长最长达54个月，期间未观察到严重不良事件。本研究证实，针对基于ASC特性与疾病病理生理学的极端临床适应证，自体ASC移植可被视为一种安全且可行的治疗手段。