Vériter Sophie, André Wivine, Aouassar Najima, Poirel Hélène Antoine, Lafosse Aurore, Docquier Pierre-Louis, Dufrane Denis
Endocrine Cell Therapy, Centre of Tissular and Cellular Therapy, Cliniques Universitaires Saint Luc, Brussels, Belgium.
Center for Human Genetics, Cliniques Universitaires Saint Luc, Université catholique de Louvain, Brussels, Belgium.
PLoS One. 2015 Oct 20;10(10):e0139566. doi: 10.1371/journal.pone.0139566. eCollection 2015.
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（ASC）的免疫调节、成骨和促血管生成特性，本研究旨在评估ASC衍生细胞疗法用于临床适应症的安全性和有效性。向17例传统疗法无效的患者提供了两种自体ASC衍生产品：（1）用于治疗骨不连的无支架成骨三维移植物；（2）用于非愈合慢性伤口皮肤重建的生物敷料。通过对最终产品的质量控制（遗传稳定性、微生物/支原体/内毒素污染）以及移植后不良事件的体内评估来研究安全性。通过以下能力评估可行性：可重复获得具有特定特征的最终基于ASC的产品、移植物制造所需的时间、生产足够材料以治疗病变的能力、移植物的手术操作以及根据医院豁免规定制造移植物的能力。对于16例患者（1例患者因骨自发愈合未接受移植），过程控制未发现微生物/支原体/内毒素污染、无明显有害基因组异常且ASC纯度最佳。每种类型的移植物均可重复获得，植入无明显延迟，手术操作始终符合手术程序和植入部位要求。长达54个月未发现严重不良事件。我们证明，自体ASC移植可被视为一种安全可行的治疗工具，用于ASC特性和疾病病理生理学的极端临床适应症。
