Comparison of the Population Capacity of Hematopoietic and Mesenchymal Stem Cells in Experimental Colitis Rat Model

Autor: Yuyuan Li, Yuqiang Nie, Yu-Jui Yvonne Wan, Jie-ying Lai, Ya-ming Wei
Rok vydání: 2009
Předmět:
Zdroj: Transplantation. 88:42-48
ISSN: 0041-1337
Popis: Inflammatory bowel disease (IBD), both ulcerative colitis and Crohn's disease (CD), is common in the western world. The estimated incidences range from 3.1 to 14.6 and 5.6 per 100,000 persons per year in North America (1) and Europe (2), respectively. Recently, the disease is reported more frequently in Asia-Pacific regions (3, 4). The causes of IBD remain obscure. Severe and continuous inflammation can disrupt the intrinsic repair system, which results in refractory ulcers in the intestine. Most patients with IBD suffer a low quality of life. There is no known cure for IBD. Present therapies aim to suppress inflammation and relieve symptoms. The goals of treatment are to induce and maintain remission, thus healing of the intestinal mucosa can occur to reconstitute the normal function. Immunosuppressants including aminosalicylates, corticosteroids, and 6-mercaptopurin are commonly used, but none of them have a curative effect. One possible treatment of IBD is bone marrow transplantation (BMT) or hematopoietic stem-cell transplantation (HSCT), which is an established technique for hematological disorders. Most clinical reports are from patients with hematological disorders who also have IBD. In 1998, Kashyap and Forman (5) first reported a case of non-Hodgkin's lymphoma with CD that had CD remission and sustained symptom free for 7 years after receiving autologous BMT. In a case of six patients with CD undergoing allogeneic BMT for myeloid leukemia, five patients were free of CD-related symptoms for longer than 1 year (6). The followed-up cases of allogeneic and autologous HSCT showed an average 7-year and 20-month remission (7). The data from 11 patients with IBD, who received allogeneic stem-cell transplantation (SCT) for treatment of myeloid leukemia and myelodysplastic syn dromes, showed that 9 of 10 patients were free from IBD, after an average follow-up of 34 months post-SCT (8). In another report of allogeneic HSCT for refractory CD, 11 of 12 patients maintained a sustained remission defined as a CD activity index less than or equal to 150 (9). In a review article, Brittan et al. (10) summarized the literature until 2007. Overall, of 33 cases of CD undergoing autologous or allogeneic BMT 29 remained in remission with transplantation-related mortality in two cases. No deaths occurred in the 14 cases transplanted primarily for the treatment of CD. These studies suggested the efficacy and safety of both allogeneic and autologous BMT in the treatment of IBD (7–11). On the basis of these results, a clinical trial to determine the value of SCT in IBD has been carried out under the supervision of the European Group for Blood and Marrow Transplantation (12). Although clinical studies showed promising results of SCT for IBD treatment, questions remain concerning the mechanism of SCT. It remains to be determined whether the colon was repaired by grafted stem cells or by colon epithelium cell. In addition, the relative importance of hematopoietic stem cells (HSCs) and mesenchymal stem cells (MSCs) in contribution to colon repair has not been fully addressed. In animal models, bone marrow-derived cells, especially MSCs, were reported to be involved in the healing process after intestinal injury and contribute to various components of the mucosa (13–15). A few histologic analyses revealed the re-population of the epithelial cells with MSCs in human gastrointestinal (GI) tract (6). However, in clinical transplantation treatment, HSCs, not MSCs, are the main source of grafted cells, the allogeneic HSCs can be collected from donor's bone marrow or peripheral blood. Collection of peripheral blood stem cell is a less invasive procedure; therefore, allogeneic peripheral blood stem cell transplantation is being used in more transplant units instead of BMT. Thus, the role of HSCs in the repair ability in IBD needs to be surveyed and defined. In this study, we transplanted HSCs or MSCs and HSCs+MSCs into experimental colitis (EC) rat model to compare their ability to populate and repair the intestinal mucosa of EC after SCT.
Databáze: OpenAIRE
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