Multiple intravenous injections of allogeneic equine mesenchymal stem cells do not induce a systemic inflammatory response but do alter lymphocyte subsets in healthy horses.
Multiple intravenous injections of allogeneic equine mesenchymal stem cells do not induce a systemic inflammatory response but do alter lymphocyte subsets in healthy horses.
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DOI：
10.1186/s13287-015-0050-0
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发表时间：
2015-04-15
影响因子：
7.5
通讯作者：
Borjesson DL
中科院分区：
文献类型：
--
作者：
Kol A;Wood JA;Carrade Holt DD;Gillette JA;Bohannon-Worsley LK;Puchalski SM;Walker NJ;Clark KC;Watson JL;Borjesson DL
静脉内（IV）注射间充质干细胞（MSC）用于治疗全身性人类疾病和病症，但不常规用于马治疗。在马中，MSC主要从脂肪组织（AT）或骨髓（BM）中分离，并通过一次或多次局部注射用于治疗骨科损伤。本研究的目的是确定对健康马多次同种异体IV注射AT衍生的MSC（AT-MSC）或BM衍生的MSC（BM-MSC）的安全性和淋巴细胞应答。我们分别将三个剂量的25 × 106来自AT或BM的同种异体MSC（每匹马总共75 × 106 MSC）注射到5匹和5匹健康马中。马在第一次MSC输注后随访35天。我们评估了宿主的炎症和免疫反应，包括白细胞总数、血清细胞因子浓度和脾淋巴细胞亚群。重复注射同种异体AT-MSCs或BM-MSCs未引起任何临床不良反应。重复BM-MSC注射导致血液CD 8 + T细胞数量增加。与注射AT-MSC的马相比，多次BM-MSC注射也增加了脾脏调节性T细胞数量，但对照组没有。这些数据表明，健康马对同种异体MSC的多次IV注射耐受良好。未记录器官毒性或全身炎症反应的临床体征或临床病理学测量结果。多次静脉注射同种异体BM-MSC后循环CD 8 + T细胞数量的增加可能表明轻度同种异体抗原导向的细胞毒性反应。同种异体MSC IV输注在病马中的安全性和有效性仍有待确定。
Intravenous (IV) injection of mesenchymal stem cells (MSCs) is used to treat systemic human diseases and disorders but is not routinely used in equine therapy. In horses, MSCs are isolated primarily from adipose tissue (AT) or bone marrow (BM) and used for treatment of orthopedic injuries through one or more local injections. The objective of this study was to determine the safety and lymphocyte response to multiple allogeneic IV injections of either AT-derived MSCs (AT-MSCs) or BM-derived MSCs (BM-MSCs) to healthy horses. We injected three doses of 25 × 106 allogeneic MSCs from either AT or BM (a total of 75 × 106 MSCs per horse) into five and five, respectively, healthy horses. Horses were followed up for 35 days after the first MSC infusion. We evaluated host inflammatory and immune response, including total leukocyte numbers, serum cytokine concentration, and splenic lymphocyte subsets. Repeated injection of allogeneic AT-MSCs or BM-MSCs did not elicit any clinical adverse effects. Repeated BM-MSC injection resulted in increased blood CD8+ T-cell numbers. Multiple BM-MSC injections also increased splenic regulatory T cell numbers compared with AT-MSC-injected horses but not controls. These data demonstrate that multiple IV injections of allogeneic MSCs are well tolerated by healthy horses. No clinical signs or clinico-pathologic measurements of organ toxicity or systemic inflammatory response were recorded. Increased numbers of circulating CD8+ T cells after multiple IV injections of allogeneic BM-MSCs may indicate a mild allo-antigen-directed cytotoxic response. Safety and efficacy of allogeneic MSC IV infusions in sick horses remain to be determined.
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影响因子：
4.3
作者：
Kang SK;Shin IS;Ko MS;Jo JY;Ra JC
通讯作者：
Ra JC
影响因子：
24
作者：
Hare, Joshua M.;Traverse, Jay H.;Henry, Timothy D.;Dib, Nabil;Strumpf, Robert K.;Schulman, Steven P.;Gerstenblith, Gary;DeMaria, Anthony N.;Denktas, Ali E.;Gammon, Roger S.;Hermiller, James B., Jr.;Reisman, Mark A.;Schaer, Gary L.;Sherman, Warren
通讯作者：
Sherman, Warren
影响因子：
5.2
作者：
Kern, Susanne;Eichler, Hermann;Bieback, Karen
通讯作者：
Bieback, Karen
影响因子：
1.8
作者：
Robbin, Melissa G.;Wagner, Bettina;de Mestre, Amanda M.
通讯作者：
de Mestre, Amanda M.
影响因子：
3.7
作者：
Isakova IA;Lanclos C;Bruhn J;Kuroda MJ;Baker KC;Krishnappa V;Phinney DG
通讯作者：
Phinney DG