Marrow Stromal Cells, Mitosis, and Neuronal Differentiation: Stem Cell and Precursor Functions

Muñoz‐Elías, Guillermo; Woodbury, Dale; Black, Ira B.

doi:10.1634/stemcells.21-4-437

Cited by 191 publications

(126 citation statements)

References 37 publications

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“…This piece of evidence, together with the fibroblastic morphology of cells, allowed us to conclude that these cells were MSCs. Neuronal differentiation of MSCs may require activation by specific exogenous factors, 19 as they were not observed expressing a neuronal phenotype after intraspinal transplantation and they probably changed to glial cells. 20 Thus, neuronal replacement in the spinal cord is feasible but requires grafting pre-differentiated stem cells or neuronal precursor cells.…”

Section: Discussionmentioning

confidence: 99%

Transplantation of a combination of autologous neural differentiated and undifferentiated mesenchymal stem cells into injured spinal cord of rats

et al. 2009

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Study design: The use of stem cells for functional recovery after spinal cord injury. Objective: The aim of this study was to evaluate the effects of a combination of autologous undifferentiated and neural-induced bone marrow mesenchymal stem cells (MSCs) on behavioral improvement in rats after inducing spinal cord injury and comparing with transplantation of undifferentiated and neural-induced MSCs alone. Setting: The study was conducted at the department of Clinical Sciences, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran. Methods: The spinal cord was injured by contusion using a Fogarty embolectomy catheter at the T8-T9 level of the spinal cord, and autologous MSCs were transplanted into the center of the developing lesion cavity, 3 mm cranial and 3 mm caudal to the cavity, at 7 days after induction of spinal cord compression injury. Results: At 5 weeks after transplantation, the presence of transplanted cells was detected in the spinal cord parenchyma using immunohistochemistry analysis. In all treatment groups (differentiated, undifferentiated and mix), there was less cavitation than lesion sites in the control group. The BassoBeattie-Bresnahan (BBB) score was significantly higher in rats transplanted with a combination of cells and in rats transplanted with neural-induced MSCs alone than in undifferentiated and control rats. Conclusion: Pre-differentiation of MSCs to neuron-like cells has a very important role in achieving the best results for functional improvement.

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Section: Discussionmentioning

confidence: 99%

Transplantation of a combination of autologous neural differentiated and undifferentiated mesenchymal stem cells into injured spinal cord of rats

et al. 2009

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“…For neurogenesis, various inducers, alone or in combination, are involved in neurocytic differentiation in vitro of MSCs. These include retinoic acid (Cho et al, 2005), DMSO and BHA (Chu et al, 2004;Lu et al, 2004), GM1 and bFGF (Dezawa et al, 2004;Zhang et al, 2004b;Munoz-Elias et al, 2003), and 2-mercaptoethanol (2-ME) (Guo et al, 2001). It was suggested that cAMP signaling pathway should be involved in neurocytic differentiation of MSCs (Suon et al, 2004;Jori et al, 2005), but it could not rule out the synergistic effect of other signaling pathways on neurogenesis of hMSCs, in regard to neural differentiation of embryonic stem cells (Kleber et al, 2005;Bainter et al, 2001;Otero et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

Ex vivo expansion and pluripotential differentiation of cryopreserved human bone marrow mesenchymal stem cells

Xiang

Zheng

Jia

et al. 2007

J. Zhejiang Univ. - Sci. B

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This study is aimed at investigating the potentials of ex vivo expansion and pluri-differentiation of cryopreservation of adult human bone marrow mesenchymal stem cells (hMSCs) into chondrocytes, adipocytes and neurocytes. Cryopreserved hMSCs were resuscitated and cultured for 15 passages, and then induced into chondrocytes, adipocytes and neurocytes with corresponding induction medium. The induced cells were observed for morphological properties and detected for expressions of type II collagen, triglyceride or neuron-specific enolase and nestin. The result showed that the resuscitated cells could differentiate into chondrocytes after exposure to transforming growth factor β 1 (TGF-β 1 ), insulin-like growth factor I (IGF-I) and vitamin C (V C ), and uniformly changed morphologically from a spindle-like fibroblastic appearance to a polygonal shape in three weeks. The induced cells were heterochromatic to safranin O and expressed cartilage matrix-procollagenal (II) mRNA. The resuscitated cells cultured in induction medium consisting of dexamethasone, 3-isobutyl-1-methylxanthine, indomethacin and IGF-I showed adipogenesis, and lipid vacuoles accumulation was detectable after 21 d. The resuscitated hMSCs were also induced into neurocytes and expressed nestin and neuron specific endolase (NSE) that were special surface markers associated with neural cells at different stage. This study suggested that the resuscitated hMSCs should be still a population of pluripotential cells and that it could be used for establishing an abundant hMSC reservoir for further experiment and treatment of various clinical diseases.

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“…24,25 Accordingly, we investigated the efficiency of neural differentiation of PFs and BT-PFs in response to neuronal differentiation medium (nDM) at a morphological level monitored by timelapse video microscopy ( Figure 5a). Initially, both PFs and BT-PFs exhibited fibroblast morphologies.…”

Section: Morphological Transformation and Marker Analysis Of Pfs And mentioning

confidence: 99%

Highly efficient multipotent differentiation of human periodontal ligament fibroblasts induced by combined BMP4 and hTERT gene transfer

et al. 2011

Gene Ther

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Because periodontal ligament (PDL) cells are reported to contain progenitor or stem cell populations, they are considered a beneficial cell source for clinical periodontal regeneration. Both bone morphogenetic protein 4 (BMP4) and human telomerase reverse transcriptase (hTERT) have essential roles in the modulation of stem cell properties. In this study we report for the first time that the combined ectopic expression of BMP4 and hTERT significantly enhanced the multipotent differentiation efficiency and capacity of human PDL fibroblasts (PFs), as shown by osteogenic, adipogenic and neurogenic differentiation in vitro, and cementum/PDL-like tissue regeneration in vivo. These findings may be attributed, at least in part, to the original upregulation of important stem cell markers, such as scleraxis, Stro-1 and CD146, and the extremely lowered threshold for BMP concentration to activate BMP signaling by enhanced basal phosphorylation levels of Smad 1/5/8. In addition, the significantly reduced expression levels of CD146 and CD90 with the presence of Noggin confirms the direct effect of BMP4 on the stem cell-like phenotype of genetically modified PF cells (BT-PFs). Furthermore, BT-PFs exhibited a high neural differentiation capacity (475%). After transplantation into NOD/SCID mice, genetically modified-PFs generated cementum/PDL-like structures on the surface of the carrier. The multipotency of these modified cells potentially provides an attractive source of stem cells for therapeutic purposes and regenerative medicine.

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Marrow Stromal Cells, Mitosis, and Neuronal Differentiation: Stem Cell and Precursor Functions

Cited by 191 publications

References 37 publications

Transplantation of a combination of autologous neural differentiated and undifferentiated mesenchymal stem cells into injured spinal cord of rats

Transplantation of a combination of autologous neural differentiated and undifferentiated mesenchymal stem cells into injured spinal cord of rats

Ex vivo expansion and pluripotential differentiation of cryopreserved human bone marrow mesenchymal stem cells

Highly efficient multipotent differentiation of human periodontal ligament fibroblasts induced by combined BMP4 and hTERT gene transfer

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