Davey Grace C, Patil Swapnil B, O'Loughlin Aonghus, O'Brien Timothy
Regenerative Medicine Institute (REMEDI) and Biosciences Building, National University of Ireland , Galway , Ireland.
Department of Medicine, Galway University Hospital (GUH) , Galway , Ireland.
Front Endocrinol (Lausanne). 2014 Jun 6;5:86. doi: 10.3389/fendo.2014.00086. eCollection 2014.
The worldwide increase in the prevalence of Diabetes mellitus (DM) has highlighted the need for increased research efforts into treatment options for both the disease itself and its associated complications. In recent years, mesenchymal stromal cells (MSCs) have been highlighted as a new emerging regenerative therapy due to their multipotency but also due to their paracrine secretion of angiogenic factors, cytokines, and immunomodulatory substances. This review focuses on the potential use of MSCs as a regenerative medicine in microvascular and secondary complications of DM and will discuss the challenges and future prospects of MSCs as a regenerative therapy in this field. MSCs are believed to have an important role in tissue repair. Evidence in recent years has demonstrated that MSCs have potent immunomodulatory functions resulting in active suppression of various components of the host immune response. MSCs may also have glucose lowering properties providing another attractive and unique feature of this therapeutic approach. Through a combination of the above characteristics, MSCs have been shown to exert beneficial effects in pre-clinical models of diabetic complications prompting initial clinical studies in diabetic wound healing and nephropathy. Challenges that remain in the clinical translation of MSC therapy include issues of MSC heterogeneity, optimal mode of cell delivery, homing of these cells to tissues of interest with high efficiency, clinically meaningful engraftment, and challenges with cell manufacture. An issue of added importance is whether an autologous or allogeneic approach will be used. In summary, MSC administration has significant potential in the treatment of diabetic microvascular and secondary complications but challenges remain in terms of engraftment, persistence, tissue targeting, and cell manufacture.
全球糖尿病（DM）患病率的上升凸显了加大对该疾病及其相关并发症治疗方案研究力度的必要性。近年来，间充质基质细胞（MSCs）因其多能性以及旁分泌血管生成因子、细胞因子和免疫调节物质的能力，成为一种新兴的再生疗法。本综述聚焦于MSCs作为再生医学在糖尿病微血管及继发性并发症中的潜在应用，并将探讨MSCs作为该领域再生疗法的挑战和未来前景。人们认为MSCs在组织修复中发挥着重要作用。近年来的证据表明，MSCs具有强大的免疫调节功能，可有效抑制宿主免疫反应的各个组成部分。MSCs还可能具有降低血糖的特性，这为这种治疗方法增添了另一个有吸引力的独特之处。通过上述特性的结合，MSCs已在糖尿病并发症的临床前模型中显示出有益效果，从而推动了在糖尿病伤口愈合和肾病方面的初步临床研究。MSCs治疗临床转化中仍然存在的挑战包括MSCs异质性问题、细胞递送的最佳方式、这些细胞高效归巢至目标组织、具有临床意义的植入以及细胞制造方面的挑战。一个更为重要的问题是将采用自体还是异体方法。总之，MSCs给药在治疗糖尿病微血管及继发性并发症方面具有巨大潜力，但在植入、持久性、组织靶向和细胞制造方面仍存在挑战。
