Transplantation of Chemical Compound-Induced Cells from Human Fibroblasts Improves Locomotor Recovery in a Spinal Cord Injury Rat Model

Abstract

The development of regenerative medicine using cell therapy is eagerly awaited for diseases such as spinal cord injury (SCI), for which there has been no radical cure. We previously reported the direct conversion of human fibroblasts into neuronal-like cells using only chemical compounds; however, it is unclear whether chemical compound-induced neuronal-like (CiN) cells are clinically functional. In this study, we partially modified the method of inducing CiN cells (termed immature CiN cells) and examined their therapeutic efficacy, in a rat model of SCI, to investigate whether immature CiN cells are promising for clinical applications. Motor function recovery, after SCI, was assessed using the Basso, Beattie, and Bresnahan (BBB) test, as well as the CatWalk analysis. We found that locomotor recovery, after SCI in the immature CiN cell-transplanted group, was partially improved compared to that in the control group. Consistent with these results, magnetic resonance imaging (MRI) and histopathological analyses revealed that nerve recovery or preservation improved in the immature CiN cell-transplanted group. Furthermore, transcriptome analysis revealed that immature CiN cells highly express hepatocyte growth factor (HGF), which has recently been shown to be a promising therapeutic agent against SCI. Our findings suggest that immature CiN cells may provide an alternative strategy for the regenerative therapy of SCI.

Improved Efficacy of Delayed Treatment with Human Bone Marrow-Derived Stromal Cells Evaluated in Rats with Spinal Cord Injury

“…In nine studies documenting transplantation of cultivated human bmSCs in rat SCI models, only two reached improvements of more than 1.5 BBB-scores. Some publications during the last decade found stronger effects with human endometrial stem cells: ∆BBB ≈ 3 [23] and neuron-like induced fibroblasts: ∆BBB = 3.1 [24]; all data points at 5 W. In the present study, the group with highest dose of fresh bmSCs reached a difference of 3.4 BBB-scores compared to saline treated controls. For bone marrow-derived stromal cells, our data support the hypothesis that non-manipulated, fresh bmSCs are therapeutically better than cells expanded in vitro; however, other sources of human stem cells may provide better alternatives for the clinical use, even with expansion in culture.…”