Selection of optimal passage of bone marrow-derived mesenchymal stem cells for stem cell therapy in patients with amyotrophic lateral sclerosis

Choi, Mi Ran; Kim, Ho; Park, Jiyoon; Lee, Tae Yong; Baik, Cheong Soon; Chai, Young Gyu; Jung, Kyoung Hwa; Park, Kyoung Sun; Roh, Wonjae; Kim, Kyung Suk; Kim, Seung Hyun

doi:10.1016/j.neulet.2010.01.054

Cited by 93 publications

(65 citation statements)

References 22 publications

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“…A source of mesenchymal stem cells like VCCs is capable of differentiating into mesenchymal and potentially even neuronal lineages [52]. In ALS models, the motor neuron degeneration triggers endogenous NPCs niches in the CNS to proliferate, migrate, and promote neurogenesis in the spinal cord as a natural response to disease [9,53]; however, the limited number of proliferative, migrated endogenous NPCs is likely insufficient to combat the progressive motor neuron degeneration associated with ALS. Taken together, our study demonstrates that VCCs have the potential to impact ALS pathogenesis by replacing lost astrocytes and preserving the hospitable environment of motor neuron for neurogenesis in spinal cord.…”

Section: Discussionmentioning

confidence: 99%

An Astrocyte Regenerative Response from Vimentin-Containing Cells in the Spinal Cord of Amyotrophic Lateral Sclerosis's Disease-Like Transgenic (G93A SOD1) Mice

et al. 2015

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The reason for regeneration in the adult spinal cord during motor neuron degeneration in amyotrophic lateral sclerosis (ALS) remains largely unknown. To this end, we studied the alteration of vimentin (a neural precursor cells marker in CNS)-containing cells (VCCs) in spinal cord during different stages of ALS used C57BL/6J G93A SOD1 transgenic mice mimicking ALS. Results showed that VCCs were mostly distributed in the ependymal zone (EZ) surrounding the central canal of spinal cord in SOD1 wild type mice; a few of VCCs were sparsely distributed in other regions. However, the number of VCCs significantly increased in the spinal cord during the onset and progression stages of ALS. They were extensively distributed in the EZ, the anterior, the lateral and the posterior horn of grey matter, particularly in the posterior horn region at the progression stage. A majority of VCCs in the anterior, the lateral and the posterior horn of grey matter (outside of EZ) generated astrocytes, but no neurons, oligodendrocytes and microgliocytes. Our results suggested that there was a potential astrocyte regenerative response to motor neuron degeneration in motor neurons-degenerated regions in the adult spinal cord during the onset and progression stages of ALS-like disease. The regenerative responses in the adult spinal cord of ALS-like mice may be a potential pathway in attempting to repair the degenerated motor neurons and restore the dysfunctional neural circuitry.

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Section: Discussionmentioning

confidence: 99%

An Astrocyte Regenerative Response from Vimentin-Containing Cells in the Spinal Cord of Amyotrophic Lateral Sclerosis's Disease-Like Transgenic (G93A SOD1) Mice

et al. 2015

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“…Passage 4 MSCs were employed for in vivo experiments in this study because MSC secretion of anti-inflammatory cytokines, neurotrophic factors, and immunomodulating agents is most optimal at early passages, gradually declining with successive passages (16). Timing of administration can additionally impact MSC efficacy and homing capacity.…”

Section: Discussionmentioning

confidence: 99%

Mesenchymal stem cells and conditioned medium avert enteric neuropathy and colon dysfunction in guinea pig TNBS-induced colitis

Robinson

Sakkal

Park

et al. 2014

American Journal of Physiology-Gastrointestinal and Liver Physi

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Robinson AM, Sakkal S, Park A, Jovanovska V, Payne N, Carbone SE, Miller S, Bornstein JC, Bernard C, Boyd R, Nurgali K. Mesenchymal stem cells and conditioned medium avert enteric neuropathy and colon dysfunction in guinea pig TNBS-induced colitis. Am J Physiol Gastrointest Liver Physiol 307: G1115-G1129, 2014. First published October 9, 2014 doi:10.1152/ajpgi.00174.2014.-Damage to the enteric nervous system (ENS) associated with intestinal inflammation may underlie persistent alterations to gut functions, suggesting that enteric neurons are viable targets for novel therapies. Mesenchymal stem cells (MSCs) offer therapeutic benefits for attenuation of neurodegenerative diseases by homing to areas of inflammation and exhibiting neuroprotective, anti-inflammatory, and immunomodulatory properties. In culture, MSCs release soluble bioactive factors promoting neuronal survival and suppressing inflammation suggesting that MSC-conditioned medium (CM) provides essential factors to repair damaged tissues. We investigated whether MSC and CM treatments administered by enema attenuate 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced enteric neuropathy and motility dysfunction in the guinea pig colon. Guinea pigs were randomly assigned to experimental groups and received a single application of TNBS (30 mg/kg) followed by 1 ϫ 10 6 human bone marrow-derived MSCs, 300 l CM, or 300 l unconditioned medium 3 h later. After 7 days, the effect of these treatments on enteric neurons was assessed by histological, immunohistochemical, and motility analyses. MSC and CM treatments prevented inflammation-associated weight loss and gross morphological damage in the colon; decreased the quantity of immune infiltrate in the colonic wall (P Ͻ 0.01) and at the level of the myenteric ganglia (P Ͻ 0.001); prevented loss of myenteric neurons (P Ͻ 0.05) and damage to nerve processes, changes in ChAT, and nNOS immunoreactivity (P Ͻ 0.05); and alleviated inflammationinduced colonic dysmotility (contraction speed; P Ͻ 0.001, contractions/min; P Ͻ 0.05). These results provide strong evidence that both MSC and CM treatments can effectively prevent damage to the ENS and alleviate gut dysfunction caused by TNBS-induced colitis.

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“…MSCs and NSCs have been used to generate immunomodulatory cells, growth factor-releasing cells, functional support cells such as glia, or GABAergic interneurons to modify MN survival and activity. Several clinical studies (Choi et al, 2010; Connick et al, 2011; Karussis et al, 2010; Mazzini et al, 2012; Xiao et al, 2015) have examined the effect of transplanting MSCs to alter the inflammatory microenvironment in the spinal cord of ALS patients. Intravenous allo-transplantation of MSCs showed migration of the cells to the pathologic lesions.…”

Section: Cell Therapy For Alsmentioning

confidence: 99%

Reverse engineering human neurodegenerative disease using pluripotent stem cell technology

Liu

Deng

2016

Brain Research

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With the technology of reprogramming somatic cells by introducing defined transcription factors that enables the generation of “induced pluripotent stem cells (iPSCs)” with pluripotency comparable to that of embryonic stem cells (ESCs), it has become possible to use this technology to produce various cells and tissues that have been difficult to obtain from living bodies. This advancement is bringing forth rapid progress in iPSC-based disease modeling, drug screening, and regenerative medicine. More and more studies have demonstrated that phenotypes of adult-onset neurodegenerative disorders could be rather faithfully recapitulated in iPSC-derived neural cell cultures. Moreover, despite the adult-onset nature of the diseases, pathogenic phenotypes and cellular abnormalities often exist in early developmental stages, providing new “windows of opportunity” for understanding mechanisms underlying neurodegenerative disorders and for discovering new medicines. The cell reprogramming technology enables a reverse engineering approach for modeling the cellular degenerative phenotypes of a wide range of human disorders. An excellent example is the study of the human neurodegenerative disease amyotrophic lateral sclerosis (ALS) using iPSCs. ALS is a progressive neurodegenerative disease characterized by the loss of upper and lower motor neurons (MNs), culminating in muscle wasting and death from respiratory failure. The iPSC approach provides innovative cell culture platforms to serve as ALS patient-derived model systems. Researchers have converted iPSCs derived from ALS patients into MNs and various types of glial cells, all of which are involved in ALS, to study the disease. The iPSC technology could be used to determine the role of specific genetic factors to track down what’s wrong in the neurodegenerative disease process in the “disease-in-a-dish” model. Meanwhile, parallel experiments of targeting the same specific genes in human ESCs could also be performed to control and to complement the iPSC-based approach for ALS disease modeling studies. Much knowledge has been generated from the study of both ALS iPSCs and ESCs. As these methods have advantages and disadvantages that should be balanced on experimental design in order for them to complement one another, combining the diverse methods would help build an expanded knowledge of ALS pathophysiology. The goals are to reverse engineer the human disease using ESCs and iPSCs, generate lineage reporter lines and in vitro disease models, target disease related genes, in order to better understand the molecular and cellular mechanisms of differentiation regulation along neural (neuronal versus glial) lineages, to unravel the pathogenesis of the neurodegenerative disease, and to provide appropriate cell sources for replacement therapy.

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Selection of optimal passage of bone marrow-derived mesenchymal stem cells for stem cell therapy in patients with amyotrophic lateral sclerosis

Cited by 93 publications

References 22 publications

An Astrocyte Regenerative Response from Vimentin-Containing Cells in the Spinal Cord of Amyotrophic Lateral Sclerosis's Disease-Like Transgenic (G93A SOD1) Mice

An Astrocyte Regenerative Response from Vimentin-Containing Cells in the Spinal Cord of Amyotrophic Lateral Sclerosis's Disease-Like Transgenic (G93A SOD1) Mice

Mesenchymal stem cells and conditioned medium avert enteric neuropathy and colon dysfunction in guinea pig TNBS-induced colitis

Reverse engineering human neurodegenerative disease using pluripotent stem cell technology

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