Autoreactive T cells induce in vitro BM mesenchymal stem cell transdifferentiation to neural stem cells

Moviglia, G.A.; Varela, Gabriela; Gaeta, C.; Brizuela, JA; Bastos, Fernanda Zettel; Saslavsky, J.

doi:10.1080/14653240600735958

Cited by 28 publications

(26 citation statements)

References 20 publications

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“…The improvements were in the range of spontaneous functional recovery except for one patient that recovered from ASIA score B to D. This study underscores that BMSCs were well tolerated (at least over the observation period of the trial) but no significant conclusions can be drawn due to the small number of patients included [113]. Similarly Saslavsky and colleagues [114,115] have started a therapeutic approach based on the generation of a controlled inflammatory microenvironment at the lesion site for the subsequent administration of autologous bone marrow mesenchymal stem cells. They cultivated BMSCs with the patient's own autoimmune T (AT) cells in order to produce neural stem cells (NSCs).…”

Section: Discussionmentioning

confidence: 49%

Neuronal repair and replacement in spinal cord injury

Bareyre

2008

Journal of the Neurological Sciences

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Section: Discussionmentioning

confidence: 49%

Neuronal repair and replacement in spinal cord injury

Bareyre

2008

Journal of the Neurological Sciences

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“…So far, three clinical studies have been published regarding the use of bone marrow MSC for spinal cord injury. In 2006, basing on their previous findings that human MSC derived from adult bone marrow can trans-differentiate into neural stem cells when co-cultured with auto-reactive T-lymphocytes [77], Moviglia et al [45](Table 1) reported clinical extension of spinal cord function in two patients when given these MSC pre-primed with anti-T cells autoserum and noted no apparent adverse effects. In 2009, Kishk et al [46] (Table 1) conducted an open label case-control study with 64 patients who had SCI within an average of 3.6 years.…”

Section: Cell-based Strategies For Treating Neuropathic Pain Associatmentioning

confidence: 99%

Cellular therapies for treating pain associated with spinal cord injury

Leung

2012

J Transl Med

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Spinal cord injury leads to immense disability and loss of quality of life in human with no satisfactory clinical cure. Cell-based or cell-related therapies have emerged as promising therapeutic potentials both in regeneration of spinal cord and mitigation of neuropathic pain due to spinal cord injury. This article reviews the various options and their latest developments with an update on their therapeutic potentials and clinical trialing.

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“…Several research groups have reported that MSC helps in tissue regeneration and repair via the release of small biomolecules (29–34) (paracrine effect) or by transdifferentiating (35–38) into the required cell types. As such, we investigated whether these mechanisms could have played a role in the viability enhancement of the UCB-MNC.…”

Section: Resultsmentioning

confidence: 99%

Intercellular cytosolic transfer correlates with mesenchymal stromal cell rescue of umbilical cord blood cell viability during ex vivo expansion

et al. 2012

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Background aims. Mesenchymal stromal cells (MSC) have been observed to participate in tissue repair and to have growth-promoting effects on ex vivo co-culture with other stem cells. Methods. In order to evaluate the mechanism of MSC support on ex vivo cultures, we performed co-culture of MSC with umbilical cord blood (UCB) mononuclear cells (MNC) (UCB-MNC). Results. Significant enhancement in cell growth correlating with cell viability was noted with MSC co-culture (defined by double-negative staining for Annexin-V and 7-AAD; P<0.01). This was associated with significant enhancement of mitochondrial membrane potential (P<0.01). We postulated that intercellular transfer of cytosolic substances between MSC and UCB-MNC could be one mechanism mediating the support. Using MSC endogenously expressing green fluorescent protein (GFP) or labeled with quantum dots (QD), we performed co-culture of UCB-MNC with these MSC. Transfer of these GFP and QD was observed from MSC to UCB-MNC as early as 24 h post co-culture. Transwell experiments revealed that direct contact between MSC and UCB-MNC was necessary for both transfer and viability support. UCB-MNC tightly adherent to the MSC layer exhibited the most optimal transfer and rescue of cell viability. DNA analysis of the viable, GFP transfer-positive UCB-MNC ruled out MSC transdifferentiation or MSC-UCB fusion. In addition, there was statistical correlation between higher levels of cytosolic transfer and enhanced UCB-MNC viability (P< 0.0001). Conclusions. Collectively, the data suggest that intercellular transfer of cytosolic materials could be one novel mechanism for preventing UCB cell death in MSC co-culture.

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Autoreactive T cells induce in vitro BM mesenchymal stem cell transdifferentiation to neural stem cells

Cited by 28 publications

References 20 publications

Neuronal repair and replacement in spinal cord injury

Neuronal repair and replacement in spinal cord injury

Cellular therapies for treating pain associated with spinal cord injury

Intercellular cytosolic transfer correlates with mesenchymal stromal cell rescue of umbilical cord blood cell viability during ex vivo expansion

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