Biology subjects

Ma, Y. H. E.

Publications and source records attributed to Ma, Y. H. E..

3 recordsLinked to original sources

bioRxiv2025

Prolonged Heat Treated Mesenchymal Precursor Cells Induce Positive Outcomes Following Transplantation in Cervical Spinal Cord Injury.

Cellular transplantation therapies have been extensively used in experimental spinal cord injury research. However, there is no consensus as to what the most effective cellular controls for the therapeutic cell of interest are. For this reason, we examined if dead cells obtained through prolonged heat treatment can act as an appropriate cellular control for intravenously injected Sca-1+ mesenchymal precursor cells (MPCs) in C5 unilateral contusion cervical spinal cord injury. This was tested in single intravenous MPCs injection alone or intravenous MPCs plus intraspinal neural stem cells (NSCs) combinatory transplantation studies. MPCs were isolated from the compact bone of FVB mice while NSCs were isolated from the subventricular zone of luciferase-GFP transgenic FVB mice. Dead MPCs were obtained by heating at 72{degrees}C for at least 12 hours. In the MPCs only transplant study, injured mice received an injection of 1x106 dead or live MPCs D1 post-injury. Mice were then sacrificed at 8 weeks post-injury. In this study, intravenous injections of dead MPCs showed no statistical difference in injured paw usage compared to live MPCs, but behavior was improved compared to the media vehicle only control at D7 and D21. In the combinatory MPCs plus NSCs transplant study, injured mice received an intravenous injection of 1x106 dead or live MPCs D1 post-injury followed by intraspinal injection of 100,000 NSCs at D3 or D7 post-injury. Another two cohorts of mice received only NSCs at D3 or D7 post-injury. Mice were then sacrificed at 6 weeks post-injury. In this study, there was no functional difference in any of the groups in the dual injection study. Morphologically, mice receiving IV injection of dead MPCs had a smaller lesion size compared to the vehicular control, but the lesion size was larger than that of the lesion size in mice receiving live MPC injection. Dead cells elicited functional and anatomical benefits for the spinal cord injured mouse. In summary, dead cells obtained through prolonged heat treatment proved to be inconsistent and not optimal for use as cellular controls for cell transplantation studies in spinal cord injury but provides positive evidence for non-transplantation based cell therapies.

neuroscience↗

bioRxiv2025

Combined Transplantation of Mesenchymal Progenitor and Neural Stem Cells to repair cervical spinal cord injury.

Mesenchymal progenitor cells (MPC) are effective in reducing tissue loss, preserving white matter and improving forelimb function after spinal cord injury (SCI) (White et al., 2016). We proposed that by preconditioning the mouse by intravenous delivery (IV) of MPCs for 24 hours following SCI that this would provide a more favorable tissue milieu for NSC intraspinal bridging transplantation at day 3 and day 7. In com-bination these transplants will provide better anatomical and functional outcomes. The intravenous MSCs would provide cell protection and reduce inflammation. NSCs would provide a tissue bridge for axonal regeneration and myelination and reconnect long tract spinal pathways. Results showed that initial protection of the injury site by IV MPCs transplantation resulted in no increased survival of the NSCs transplanted at Day 7. However, integration of transplanted NSCs was increased at the Day 3 time point indicating MPCs influence very early immune signaling. We show in this study that MPC transplantation resulted in a co-operative NSC cell survival improvement at Day 3 post SCI. In addition to increased NSC survival at day 3 there was an increase in NSC derived mature oligodendrocytes at this early time point. In vitro analysis confirmed MPC driven oligodendrocyte differentiation which was statistically increased when compared to control NSC only cultures. These observations provide important information about the combination, delivery, and timing of two cellular therapies in treating SCI. This study provides important new data on understanding the MPC inflammatory signaling within the host tissue and time points for cellular transplantation survival and oligodendroglia differentiation. These results demonstrate that MPC transplantation can alter the therapeutic window for intraspinal transplantation by controlling both the circulating inflammatory response and local tissue milieu.

neuroscience↗

bioRxiv2025

Efficacy of Deferoxamine Mesylate in Serum and Serum-Free Media: Adult Schwann Cell Survival Following Hydrogen Peroxide Induced Cell Death

Schwann cell (SC) transplantation shows promise in treating spinal cord injury as a pro-regenerative agent to allow host endogenous neurons to bridge over the lesion. However, SC transplants face significant oxidative stress facilitated by ROS in the lesion leading to poor survival. Deferoxamine Mesylate (DFO) is a neuroprotection agent shown to reduce H2O2 induced cell death in serum containing conditions, here we show that DFO is not necessary to induce neuroprotection under serumfree conditions by cell survival quantification and phenotypic analysis via immunohistochemistry, Hif1a and collagen IV quantification via whole cell corrected total cell fluorescence, and cell death transcript changes via RT-qPCR. Our results indicate survival of SC regardless of DFO pretreatment in serum-free conditions and an increased survival facilitated by DFO in serum containing conditions. Furthermore, our results showed strong nuclear expression of Hif1a in serum-free conditions regardless of DFO pretreatment and a nuclear expression of Hif1a in DFO treated SCs in serum conditions. Transcriptomic analysis reveals upregulation of autophagy transcripts in SCs grown in serum-free media relative to SCs in serum conditions, with and without DFO and H2O2. Thus, indicating a pro-repair and regenerative state of the SCs in serum free conditions. Overall, results indicate the protectiveness of chemically defined medium in enhancing SC survival against ROS induced cell death in vitro.

neuroscience↗