El-Badri Nagwa S, Maheshwari Akhil, Sanberg Paul R
Center for Excellence for Aging and Brain Repair, Department of Neurosurgery, College of Medicine, University of South Florida, Tampa, FL 33612, USA.
Stem Cells Dev. 2004 Oct;13(5):463-72. doi: 10.1089/scd.2004.13.463.
Autoimmune diseases afflict more than 3% of the U.S. population. Current therapy for mild to moderate cases is symptomatic, however advanced cases suffer high morbidity and mortality. Advanced patients have benefited from stem cell therapy in the form of bone marrow transplantation in conjunction with high-dose cytotoxic therapy. Broader application of stem cell therapy requires better understanding of how adult stem cells affect development and foster treatment of autoimmune pathologies, and of better ways to manipulate the host immune responses. While extensive research documents the role of hematopoietic stem cells (HSCs) in autoimmune disease, few studies have addressed if and how mesenchymal stem cells (MSCs) contribute to their etiopathology. Recent characterization of MSCs and their role in hematopoiesis and immune modulation suggest that their potential for cell therapy extends beyond their traditional accessory function in HSC engraftment. MSCs contribute significantly to tissue restructuring and immune functioning, in addition to facilitating durable, long-lasting stem cell engraftment. MSCs are relatively easy to obtain and expand in in vitro cultures, rendering them a prime candidate for genetic manipulations for stem cell therapy. They have the potential to differentiate into multiple lineages such as osteoblasts, adipose tissue, cartilage, tendon, and stromal cells. The role of MSCs for autoimmune disease therapy could thus be based both on immune function modulation and contribution to hematopoiesis. In this review, we examine the biology of MSCs, and their potential for cell therapy of autoimmune disease.
自身免疫性疾病折磨着超过3%的美国人口。目前针对轻度至中度病例的治疗只是对症治疗,然而重症病例的发病率和死亡率很高。重症患者已从干细胞疗法中受益,这种疗法是以骨髓移植结合大剂量细胞毒性疗法的形式。干细胞疗法的更广泛应用需要更好地理解成体干细胞如何影响发育并促进自身免疫性疾病的治疗,以及更好地操控宿主免疫反应的方法。虽然大量研究记录了造血干细胞(HSCs)在自身免疫性疾病中的作用,但很少有研究探讨间充质干细胞(MSCs)是否以及如何在其病因病理学中发挥作用。最近对MSCs的特性及其在造血和免疫调节中的作用的研究表明,它们在细胞治疗方面的潜力超出了其在HSC植入中的传统辅助功能。除了促进持久、长期的干细胞植入外,MSCs对组织重塑和免疫功能也有显著贡献。MSCs相对容易在体外培养中获得和扩增,使其成为干细胞治疗基因操作的主要候选对象。它们有分化为多种谱系细胞的潜力,如成骨细胞、脂肪组织、软骨、肌腱和基质细胞。因此,MSCs在自身免疫性疾病治疗中的作用可能基于免疫功能调节和对造血的贡献。在这篇综述中,我们研究了MSCs的生物学特性及其在自身免疫性疾病细胞治疗中的潜力。