Association of intravenous administration of human Muse cells with deficit amelioration in a rat model of spinal cord injury

Abstract

OBJECTIVEMultilineage-differentiating stress-enduring (Muse) cells are pluripotent stem cells, which can be harvested from the bone marrow. After transplantation, Muse cells can migrate to an injured site of the body and exert repair effects. However, it remains unknown whether Muse cell transplantation can be an effective treatment in spinal cord injury (SCI).METHODSThe authors used a rat model of thoracic spinal cord contusion injury. For Muse cell transplantation, the clinical product CL2020 containing 300,000 Muse cells was administered intravenously 1 day after midthoracic SCI. Animals were divided into CL2020 (n = 11) and vehicle-treated (n = 15) groups. Behavioral and histological evaluations were conducted over a period of 8 weeks to see whether intravenous CL2020 administration provided therapeutic effects for SCI. The effects of human-selective diphtheria toxin on reversion of the therapeutic effects of CL2020 were also investigated.RESULTSHindlimb motor function significantly improved after CL2020 transplantations. Importantly, the effects were reverted by the human-selective diphtheria toxin. In immunohistochemical analyses, the cystic cavity formed after the injury was smaller in the CL2020 group. Furthermore, higher numbers of descending 5-hydroxytryptamine (5-HT) fibers were preserved distal to the injury site after CL2020 administration. Eight weeks after the injury, Muse cells in CL2020 were confirmed to differentiate most predominantly into neuronal cells in the injured spinal cord.CONCLUSIONSFollowing SCI, Muse cells in CL2020 can reach the injured spinal cord after intravenous administration and differentiate into neuronal cells. Muse cells in CL2020 facilitated nerve fiber preservation and exerted therapeutic potential for severe SCI.

Multilineage-Differentiating Stress-Enduring Cells: A Powerful Tool for Tissue Damage Repair

“…To date, Muse cells have been used in neurological diseases [63,66,[107][108][109][110][111][112], cardiac systemic diseases [39,49,55,75,[113][114][115][116], renal diseases [40,99,117], dermatological diseases [44,78,[118][119][120], liver diseases [29,41,67,101,121], and other diseases to demonstrate their desirable effects in treating and repairing damaged tissues. In these disease models, Muse cells can migrate to the lesion site and spontaneously differentiate into histocompatible cells such as neurons (ectoderm) [43,111,122], cardiomyocytes (mesoderm) [115,123], glomerulocytes (mesoderm) [40,117], vascular endothelial cells (mesoderm) [34,120]and hepatocytes (entoderm) [41,101,121].…”

Multilineage-Differentiating Stress-Enduring Cells (Muse Cells): An Easily Accessible, Pluripotent Stem Cell Niche with Unique and Powerful Properties for Multiple Regenerative Medicine Applications

“…In fact, after SCI, spinal cord structural preservation was observed. Subsequently, Muse cells were differentiated into neural cells, resulting in the regeneration of the lesioned spinal cord parenchyma [ 67 ]. This supports Muse cells’ neural cell loss restoring properties in a spinal cord injury model.…”

Muse cells: ushering in a new era of stem cell-based therapy for stroke

“…So far, Muse cells have been used in neurological disorders [55][56][57][58], acute myocardial infarction [59], adriamycin nephropathy [60], diabetic skin ulcers [61], and liver fibrosis [35]. In these disease models, Muse cells could migrate to lesion sites and spontaneously differentiate into tissue-compatible cells, such as neurons (ectoderm) [6,12,[55][56][57][58]62], cardiac cells (mesoderm) [59], glomerular cells (mesoderm) [60], vascular endothelial cells (mesoderm) [61] and hepatocytes (entoderm) [35]. Actually, although the differentiation rate is generally very low, Muse cells have spontaneous triploblastic differentiation ability in vitro [26,62].…”