Department of Plastic and Reconstructive Surgery, Hand Surgery and Burn Centre, Medical Faculty, Pauwelsstrasse, Aachen, Germany.
Department for Orthopaedics and Trauma Surgery, Medical Faculty, Heinrich-Heine-University Düsseldorf, Moorenstrasse, Düsseldorf, Germany.
PLoS One. 2020 Apr 16;15(4):e0230265. doi: 10.1371/journal.pone.0230265. eCollection 2020.
Autologous adipose tissue (AT) transfer has gained widespread acceptance and is used for a broad variety of regenerative clinical indications. It is assumed that the successful outcome of AT transfer essentially depends on the amount of autocrine-generated growth factors (GF). It is supposed that several GF enhance and improve the anatomic and functional integration of the transplanted AT grafts at the site of implantation. In the present study we have investigated for the first time the correlation between the concentration of GF of freshly isolated AT and the proliferation and migration capacity of mesenchymal stroma cells (MSCs) derived from the respective AT sample. We here show that the proliferation and migration capacity of MSCs strongly depends on the GF content of the AT the cells were isolated from but in an inversely proportional manner. The lower the GF content of an AT sample was, the higher was the proliferation and migration capacity of the respective MSC population contained in the AT and vice versa. Furthermore, we found that supplementation with recombinant GFs only in the case of AT samples with low but not with higher growth factor contents led to a significant enhancement of proliferation and migration of the AT-resident MSCs. As we further show, this inefficiency of GFs to enhance MSC proliferation and migration in AT samples with high GF contents indicates a GF-mediated negative feedback mechanism leading to an impaired GF signaling in MSC obtained from those AT samples. Our results might explain why the successful use of AT grafting is frequently limited by low and unpredictable survival rates, and we suggest to use the knowledge of GF content of harvested AT as a predictive clinical parameter for risk assessment of the therapeutic outcome of autologous AT transfer.
自体脂肪组织 (AT) 移植已被广泛接受,并用于多种再生临床适应症。人们认为 AT 移植的成功结果主要取决于自分泌产生的生长因子 (GF) 的数量。据推测,几种 GF 可增强和改善移植 AT 移植物在植入部位的解剖和功能整合。在本研究中,我们首次研究了新鲜分离的 AT 中的 GF 浓度与源自相应 AT 样本的间充质基质细胞 (MSC) 的增殖和迁移能力之间的相关性。我们在这里表明,MSC 的增殖和迁移能力强烈依赖于其分离自的 AT 的 GF 含量,但呈反比关系。AT 样本的 GF 含量越低,包含在 AT 中的相应 MSC 群体的增殖和迁移能力越高,反之亦然。此外,我们发现,仅在 GF 含量较低的 AT 样本中补充重组 GF 会导致 AT 驻留 MSC 的增殖和迁移显著增强,而在 GF 含量较高的 AT 样本中则不会。正如我们进一步表明的那样,GF 无法增强 GF 含量较高的 AT 样本中 MSC 的增殖和迁移,这表明 GF 介导的负反馈机制导致从这些 AT 样本中获得的 MSC 的 GF 信号受损。我们的研究结果可能解释了为什么 AT 移植的成功应用经常受到低且不可预测的存活率的限制,我们建议将收获的 AT 的 GF 含量的知识用作评估自体 AT 移植治疗效果的风险的预测临床参数。