Defining human mesenchymal stem cell efficacy in vivo.
Defining human mesenchymal stem cell efficacy in vivo.
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DOI：
10.1186/1476-9255-7-51
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发表时间：
2010-10-25
期刊：
影响因子：
--
通讯作者：
Caplan AI
中科院分区：
文献类型：
--
作者：
Bonfield TL;Nolan Koloze MT;Lennon DP;Caplan AI
同种异体人间充质干细胞（hMSC）可以抑制移植物抗宿主病（GvHD），并且在人类和动物疾病模型中的中风、梗塞、脊髓损伤、半月板再生、肌腱炎、急性肾衰竭和心脏病中具有深刻的抗炎和再生能力。hMSC的疗效和体内最终反应存在显着的临床差异。基于hMSC的治疗的挑战是确定hMSC在体内的功效。可以提供对hMSC体内生物活性的深入了解的模型将提供区分hMSC用于临床用途的手段。hMSC的功能已被描述为通过产生生物活性因子的再生和营养功能。再生成分涉及hMSC祖细胞分化的多潜能性。由hMSC产生的分泌因子是环境和损伤特异性的，为体内反应提供独特的小生境。这些生物活性因子是抗瘢痕形成、血管生成、抗凋亡以及再生的。此外，从免疫学的角度来看，hMSC可以避免宿主免疫应答，提供异种应用。为了研究hMSCs在体内的免疫调节作用，我们使用了卵清蛋白激发的急性哮喘模型。这是一种快速的3周体内肺部炎症模型，具有容易获得的测量hMSC有效性的方法。我们的数据显示，传统陶瓷立方体评分与由于卵清蛋白激发引起的hMSC细胞募集衰减之间存在直接相关性。这些研究的结果验证了hMSC的体内免疫调节剂有效性，并支持卵清蛋白模型作为hMSC效力和功效的体内模型的潜在用途。我们的数据也支持未来探索hMSCs作为治疗哮喘相关气道炎症的替代疗法的方向。
Allogeneic human mesenchymal stem cells (hMSCs) can suppress graft versus host disease (GvHD) and have profound anti-inflammatory and regenerative capacity in stroke, infarct, spinal cord injury, meniscus regeneration, tendinitis, acute renal failure, and heart disease in human and animal models of disease. There is significant clinical hMSC variability in efficacy and the ultimate response in vivo. The challenge in hMSC based therapy is defining the efficacy of hMSC in vivo. Models which may provide insight into hMSC bioactivity in vivo would provide a means to distinguish hMSCs for clinical utility. hMSC function has been described as both regenerative and trophic through the production of bioactive factors. The regenerative component involves the multi-potentiality of hMSC progenitor differentiation. The secreted factors generated by the hMSCs are milieu and injury specific providing unique niches for responses in vivo. These bioactive factors are anti-scarring, angiogenic, anti-apoptotic as well as regenerative. Further, from an immunological standpoint, hMSC's can avoid host immune response, providing xenographic applications. To study the in vivo immuno-regulatory effectiveness of hMSCs, we used the ovalbumin challenge model of acute asthma. This is a quick 3 week in vivo pulmonary inflammation model with readily accessible ways of measuring effectiveness of hMSCs. Our data show that there is a direct correlation between the traditional ceramic cube score to hMSCs attenuation of cellular recruitment due to ovalbumin challenge. The results from these studies verify the in vivo immuno-modulator effectiveness of hMSCs and support the potential use of the ovalbumin model as an in vivo model of hMSC potency and efficacy. Our data also support future directions toward exploring hMSCs as an alternative therapeutic for the treatment of airway inflammation associated with asthma.
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DOI：
10.4049/jimmunol.181.1.235
发表时间：
2008-07-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Bonfield TL;Thomassen MJ;Farver CF;Abraham S;Koloze MT;Zhang X;Mosser DM;Culver DA
通讯作者：
Culver DA
影响因子：
4.2
作者：
Allay, JA;Dennis, JE;Gerson, SL
通讯作者：
Gerson, SL
DOI：
10.1152/ajplung.00219.2005
发表时间：
2006-05-01
影响因子：
4.9
作者：
Careau, É;Proulx, LI;Bissonnette, ÉY
通讯作者：
Bissonnette, ÉY
影响因子：
4
作者：
Caplan, Arnold I.;Dennis, James E.
通讯作者：
Dennis, James E.
影响因子：
82.9
作者：
Horwitz, EM;Prockop, DJ;Brenner, MK
通讯作者：
Brenner, MK