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Abstract：
BACKGROUND: Bone marrow transplantation (BMT) can be applied to both hematopoietic and nonhematopoietic diseases; nonetheless, it still comes with a number of challenges and limitations that contribute to treatment failure. Bearing this in mind, a possible way to increase the success rate of BMT would be cotransplantation of mesenchymal stem cells (MSCs) and hematopoietic stem cells (HSCs) to improve the bone marrow niche and secrete molecules that enhance the hematopoietic engraftment.
OBJECTIVE: To analyze HSC and MSC characteristics and their interactions through cotransplantation in murine models.
METHODS: We searched for original articles indexed in PubMed and Scopus during the last decade that used HSC and MSC cotransplantation and in vivo BMT in animal models while evaluating cell engraftment. We excluded in vitro studies or studies that involved graft versus host disease or other hematological diseases and publications in languages other than English. In PubMed, we initially identified 555 articles and after selection, only 12 were chosen. In Scopus, 2010 were identified, and six were left after the screening and eligibility process.
RESULTS: Of the 2565 articles found in the databases, only 18 original studies met the eligibility criteria. HSC distribution by source showed similar ratios, with human umbilical cord blood or animal bone marrow being administered mainly with a dose of 1 × 107 cells by intravenous or intrabone routes. However, MSCs had a high prevalence of human donors with a variety of sources (umbilical cord blood, bone marrow, tonsil, adipose tissue or fetal lung), using a lower dose, mainly 106 cells and ranging 104 to 1.5 × 107 cells, utilizing the same routes. MSCs were characterized prior to administration in almost every experiment. The recipient used was mostly immunodeficient mice submitted to low-dose irradiation or chemotherapy. The main technique of engraftment for HSC and MSC cotransplantation evaluation was chimerism, followed by hematopoietic reconstitution and survival analysis. Besides the engraftment, homing and cellularity were also evaluated in some studies.
CONCLUSIONS: The preclinical findings validate the potential of MSCs to enable HSC engraftment in vivo in both xenogeneic and allogeneic hematopoietic cell transplantation animal models, in the absence of toxicity.
OBJECTIVE: To analyze HSC and MSC characteristics and their interactions through cotransplantation in murine models.
METHODS: We searched for original articles indexed in PubMed and Scopus during the last decade that used HSC and MSC cotransplantation and in vivo BMT in animal models while evaluating cell engraftment. We excluded in vitro studies or studies that involved graft versus host disease or other hematological diseases and publications in languages other than English. In PubMed, we initially identified 555 articles and after selection, only 12 were chosen. In Scopus, 2010 were identified, and six were left after the screening and eligibility process.
RESULTS: Of the 2565 articles found in the databases, only 18 original studies met the eligibility criteria. HSC distribution by source showed similar ratios, with human umbilical cord blood or animal bone marrow being administered mainly with a dose of 1 × 107 cells by intravenous or intrabone routes. However, MSCs had a high prevalence of human donors with a variety of sources (umbilical cord blood, bone marrow, tonsil, adipose tissue or fetal lung), using a lower dose, mainly 106 cells and ranging 104 to 1.5 × 107 cells, utilizing the same routes. MSCs were characterized prior to administration in almost every experiment. The recipient used was mostly immunodeficient mice submitted to low-dose irradiation or chemotherapy. The main technique of engraftment for HSC and MSC cotransplantation evaluation was chimerism, followed by hematopoietic reconstitution and survival analysis. Besides the engraftment, homing and cellularity were also evaluated in some studies.
CONCLUSIONS: The preclinical findings validate the potential of MSCs to enable HSC engraftment in vivo in both xenogeneic and allogeneic hematopoietic cell transplantation animal models, in the absence of toxicity.
摘要：
背景：骨髓移植（BMT）可以应用于造血和非造血疾病；尽管如此，它仍然伴随着许多挑战和限制,导致治疗失败.记住这一点，增加BMT成功率的可能方法是间充质干细胞（MSCs）和造血干细胞（HSCs）的共移植，以改善骨髓生态位并分泌增强造血植入的分子。
目的：分析小鼠模型中HSC和MSC的特性及其相互作用。
方法：我们搜索了过去十年在PubMed和Scopus中索引的原始文章，这些文章使用HSC和MSC共移植以及在动物模型中进行体内BMT，同时评估细胞移植。我们排除了体外研究或涉及移植物抗宿主病或其他血液系统疾病的研究以及英语以外语言的出版物。在PubMed中,我们最初确定了555篇文章，经过选择，只有12人被选中。在Scopus,2010年被确定，筛选和资格程序后剩下6人。
结果：在数据库中找到的2565篇文章中，只有18项原始研究符合资格标准.按来源划分的HSC分布显示出相似的比率，人脐带血或动物骨髓主要通过静脉内或体内途径以1×107个细胞的剂量给药。然而,MSCs在人类捐献者中的患病率很高，来源多种多样（脐带血，骨髓,扁桃体,脂肪组织或胎儿肺)，使用较低的剂量，主要是106个细胞，范围为104到1.5×107个细胞，使用相同的路线。在几乎每个实验中,在施用之前表征MSC。使用的受体主要是接受低剂量照射或化疗的免疫缺陷小鼠。移植用于HSC和MSC共移植评估的主要技术是嵌合体，然后进行造血重建和生存分析。除了雕刻，归巢和细胞性也在一些研究中进行了评估。
结论：临床前研究结果验证了MSCs在异种和异基因造血细胞移植动物模型中体内移植HSC的潜力，在没有毒性的情况下。
目的：分析小鼠模型中HSC和MSC的特性及其相互作用。
方法：我们搜索了过去十年在PubMed和Scopus中索引的原始文章，这些文章使用HSC和MSC共移植以及在动物模型中进行体内BMT，同时评估细胞移植。我们排除了体外研究或涉及移植物抗宿主病或其他血液系统疾病的研究以及英语以外语言的出版物。在PubMed中,我们最初确定了555篇文章，经过选择，只有12人被选中。在Scopus,2010年被确定，筛选和资格程序后剩下6人。
结果：在数据库中找到的2565篇文章中，只有18项原始研究符合资格标准.按来源划分的HSC分布显示出相似的比率，人脐带血或动物骨髓主要通过静脉内或体内途径以1×107个细胞的剂量给药。然而,MSCs在人类捐献者中的患病率很高，来源多种多样（脐带血，骨髓,扁桃体,脂肪组织或胎儿肺)，使用较低的剂量，主要是106个细胞，范围为104到1.5×107个细胞，使用相同的路线。在几乎每个实验中,在施用之前表征MSC。使用的受体主要是接受低剂量照射或化疗的免疫缺陷小鼠。移植用于HSC和MSC共移植评估的主要技术是嵌合体，然后进行造血重建和生存分析。除了雕刻，归巢和细胞性也在一些研究中进行了评估。
结论：临床前研究结果验证了MSCs在异种和异基因造血细胞移植动物模型中体内移植HSC的潜力，在没有毒性的情况下。
