Department of Large Animal Clinical Sciences, Texas A&M University, College Station, TX, USA.
Department of Molecular and Cellular Medicine, Institute for Regenerative Medicine, Texas A&M Health Science Center, College Station, TX, USA.
Stem Cell Res Ther. 2018 Nov 8;9(1):295. doi: 10.1186/s13287-018-1037-4.
We recently demonstrated that intracellular xenogen-contaminated autologous MSCs (FBS) and non-xenogen-contaminated allogeneic (ALLO) MSCs caused an adverse clinical response after repeated intra-articular injection in horses, whereas autologous (AUTO) MSCs did not. Our current objective was to use clinical data from the previous study to compare MSC stemness against adverse response indicated by synovial total nucleated cell count (TNCC) following intra-articular MSC injection.
Stemness, quantified by a trilineage differentiation (TLD) score; immunomodulation, quantified by mixed lymphocyte reactions (MLRs); and degree of MHCI expression, quantified by mean fluorescent intensity (MFI); were correlated to the synovial TNCC 24 h after naïve and primed injection.
There was a trend of a negative correlation (p = 0.21, r = - 0.44) between TLD score and TNCC after primed injection in the ALLO group. Within the ALLO group only, there was a significant positive correlation (p = 0.05, r = 0.77) between MHCI MFI and TNCC after naïve injection and a trend (p = 0.16, r = 0.49) of a positive association of MHCI MFI to TNCC after primed injection. Within the FBS group only, there was a positive correlation (p = 0.04, r = 1) between TNCC and lymphocyte proliferation after both injections.
The trend of a negative correlation of TLD score and TNCC in the ALLO, but not the FBS group, together with the association of MHCI expression and TNCC in the ALLO group, indicates that improved stemness is associated with reduced MSC immunogenicity. When inflammation was incited by xenogen, there was a strong correlation of lymphocyte activation in vitro to adverse response in vivo, confirming that MLRs in vitro reflect MSC immunomodulatory activity in vivo. The relationship of stemness in vitro, suppression of lymphocyte activation in vitro, MHCI expression in vitro, and clinical response in vivo should be further investigated.
我们最近证明，在马中反复关节内注射细胞内异种污染的自体间充质干细胞（FBS）和非异种污染的同种异体（ALLO）间充质干细胞后，会引起不良的临床反应，而自体间充质干细胞（AUTO）则不会。我们目前的目标是使用先前研究中的临床数据，比较间充质干细胞的干性与关节内注射间充质干细胞后滑膜总核细胞计数（TNCC）所指示的不良反应。
通过三系分化（TLD）评分来量化干性；通过混合淋巴细胞反应（MLR）来量化免疫调节；通过平均荧光强度（MFI）来量化 MHC I 表达程度；并将其与注射后 24 小时的滑膜 TNCC 相关联。
在 ALLO 组中，初次和预注射后 TLD 评分与 TNCC 之间呈负相关趋势（p = 0.21，r = -0.44）。仅在 ALLO 组中，初次注射后 MHCI MFI 与 TNCC 之间存在显著正相关（p = 0.05，r = 0.77），而预注射后 MHCI MFI 与 TNCC 之间存在正相关趋势（p = 0.16，r = 0.49）。仅在 FBS 组中，初次和预注射后 TNCC 与淋巴细胞增殖之间存在正相关（p = 0.04，r = 1）。
TLD 评分与 TNCC 在 ALLO 但不在 FBS 组中呈负相关的趋势，以及 MHC I 表达与 ALLO 组中 TNCC 的关联表明，提高干性与降低间充质干细胞的免疫原性有关。当异种污染引起炎症时，体外淋巴细胞激活与体内不良反应之间存在强烈的相关性，证实了体外 MLR 反映了体内间充质干细胞的免疫调节活性。体外干性、体外淋巴细胞激活抑制、体外 MHC I 表达与体内临床反应之间的关系应进一步研究。
