Lowering the concentration affects the migration and viability of intracerebroventricular-delivered human mesenchymal stem cells

Abstract

Due to their widely known therapeutic benefits, mesenchymal stem cells have been proposed as a novel treatment option for a wide range of diseases including Alzheimer's disease. To maximize these benefits, critical factors such as delivery route, cell viability, and cell migration must be accounted for. Out of the various delivery routes to the brain, the intracerebroventricular (ICV) route stands out due to the widespread distribution that can occur via cerebrospinal fluid flow. The major objective of this present study was to observe how altering cell concentration influences the migration and viability of human umbilical cord blood derived-mesenchymal stem cells (hUCB-MSCs), delivered via ICV injection, in the brains of wild-type (WT) mice. C3H/C57 WT mice were divided into three groups and were injected with 1 × 10 hUCB-MSCs suspended in varying volumes: high (3 μl), middle (5 μl), and low (7 μl) concentrations, respectively. Lowering the concentration increased the migratory capabilities and elevated the viability of hUCB-MSCs. These results suggest that cell concentration can affect the physiological state of hUCB-MSCs, and thus the extent of therapeutic efficacy that can be achieved.

Ethionamide Preconditioning Enhances the Proliferation and Migration of Human Wharton’s Jelly-Derived Mesenchymal Stem Cells

“…Preconditioning with ethionamide enhanced the migration ability of MSCs, and CXCR4 and CXCL12 were involved in this process ( Figure 4 ). In previous studies, the administration route and dosage were optimized to acquire even distribution of the transplanted MSCs in both canine and mouse models [ 53 , 54 ]. Based on these findings, MSCs were injected into the lateral ventricle of the mouse brain and ETH-MSCs demonstrated a consistently higher migration ability compared to that of naive MSCs in vivo.…”

“…However, few studies have explored how the survival of these preconditioned MSCs are altered following transplantation into the brain. In particular, most human MSCs transplanted into the mouse brain are barely detectable by day 7 post-transplantation [ 39 , 53 , 65 ]. As shown in Figure 5 , the survival of ETH-MSCs was greater than that of naïve MSCs in the mouse brain.…”

“…Optical imaging (IVIS Spectrum In Vivo Imaging System, Perkin Elmer, Waltham, MA, USA) was performed after one week following the injection. Whole brain samples were harvested and divided into four regions as described previously [ 53 ] to investigate the migratory abilities of MSCs. The survival of injected MSCs was confirmed by Alu-qPCR seven days post- injection.…”

Intrathecal Injection in a Rat Model: A Potential Route to Deliver Human Wharton’s Jelly-Derived Mesenchymal Stem Cells into the Brain

“…First, a previous study from our group showed that the injection concentration can affect the distribution of MSCs after injecting stem cells via the intracerebroventricular route. At higher concentrations, MSCs tended to aggregate, forming clumps, whereas at lower concentrations, MSCs were easily washed out via CSF flow [14]. Second, the cell dose may affect the migration of MSCs towards the brain.…”

“…Optimizing the administration dose and improving the therapeutic efficacy of MSCs must be considered in order to maximize clinical efficacy [14]. Choosing the optimal delivery route is especially important for CNS diseases [15].…”