Neuro-glial differentiation of human bone marrow stem cells in vitro

Bossolasco, Patrizia; Cova, Lidia; Calzarossa, Cinzia; Rimoldi, Sara Giordana; Borsotti, Chiara; Deliliers, Giorgio Lambertenghi; Silani, Vincenzo; Soligo, Davide; Polli, E.

doi:10.1016/j.expneurol.2004.12.013

Cited by 187 publications

(131 citation statements)

References 56 publications

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“…Moreover, functional neuronal differentiation is accompanied by comprehensive upregulation of genes involved in synaptic transmission and long-term potentialization [57]. Furthermore, differentiation in vitro cannot be explained by the occurrence of fusion, and newer induction protocols have shifted from the initial use of chemical stressors to the more ''physiologic'' signaling molecules such as neurotrophic factors or other cytokines [58][59][60].…”

Section: The Controversy Of Msc Transdifferentiationmentioning

confidence: 99%

Introducing Transcription Factors to Multipotent Mesenchymal Stem Cells: Making Transdifferentiation Possible

2009

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Multipotent mesenchymal stem cells (MSCs) represent a promising autologous source for regenerative medicine. Because MSCs can be isolated from adult tissues, they represent an attractive cell source for autologous transplantation. A straightforward therapeutic strategy in the field of stem cell-based regenerative medicine is the transplantation of functional differentiated cells as cell replacement for the lost or defective cells affected by disease. However, this strategy requires the capacity to regulate stem cell differentiation toward the desired cell fate. This therapeutic approach assumes the capability to direct MSC differentiation toward diverse cell fates, including those outside the mesenchymal lineage, a process termed transdifferentiation. The capacity of MSCs to undergo functional transdifferentiation has been questioned over the years. Nonetheless, recent studies support that genetic manipulation can serve to promote transdifferentiation. Specifically, forced expression of certain transcription factors can lead to reprogramming and alter cell fate. Using such a method, fully differentiated lymphocytes have been reprogrammed to become macrophages and, remarkably, somatic cells have been reprogrammed to become embryonic stem-like cells. In this review, we discuss the past and current research aimed at transdifferentiating MSCs, a process with applications that could revolutionize regenerative medicine.

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Section: The Controversy Of Msc Transdifferentiationmentioning

confidence: 99%

Introducing Transcription Factors to Multipotent Mesenchymal Stem Cells: Making Transdifferentiation Possible

2009

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“…Subpopulations of cells residing within adult liver (Alison and Sarraf 1998), intestine (Potten 1998), skin/hair-follicles (Fernandes, McKenzie et al 2004;Amoh, Li et al 2005), and bone marrow (Jiang, Jahagirdar et al 2002;Jiang, Vaessen et al 2002) express neuroectodermal or neural crest cell markers in vitro and/or in vivo. Similarly, adult bone marrow-derived mesodermal stromal cells (MSC) display neurogenic properties (Woodbury, Schwarz et al 2000;Jiang, Jahagirdar et al 2002;Jiang, Vaessen et al 2002;Woodbury, Reynolds et al 2002;Dezawa, Kanno et al 2004;Hermann, Gastl et al 2004;Bonilla, Silva et al 2005;Bossolasco, Cova et al 2005;Hermann, Maisel et al 2006) including the ability to fire action potentials and respond to neurotransmitters, including GABA, glycine, and glutamate (Wislet-Gendebien, Hans et al 2005). …”

Section: Introductionmentioning

confidence: 99%

Autologous transplants of Adipose-Derived Adult Stromal (ADAS) cells afford dopaminergic neuroprotection in a model of Parkinson's disease

McCoy

Martinez

Ruhn

et al. 2008

Experimental Neurology

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Adult adipose contains stromal progenitor cells with neurogenic potential. However, the stability of neuronal phenotypes adopted by Adipose-Derived Adult Stromal (ADAS) cells and whether terminal neuronal differentiation is required for their consideration as alternatives in cell replacement strategies to treat neurological disorders is largely unknown. We investigated whether in vitro neural induction of ADAS cells determined their ability to neuroprotect or restore function in a lesioned dopaminergic pathway. In vitro-expanded naïve or differentiated ADAS cells were autologously transplanted into substantia nigra 1-week after an intrastriatal 6-hydroxydopamine injection. Neurochemical and behavioral measures demonstrated neuroprotective effects of both ADAS grafts against 6-hydroxydopamine-induced dopaminergic neuron death, suggesting that pre-transplantation differentiation of the cells does not determine their ability to survive or neuroprotect in vivo. Therefore, we investigated whether equivalent protection by naïve and neurally-induced ADAS grafts resulted from robust in situ differentiation of both graft types into dopaminergic fates. Immunohistological analyses revealed that ADAS cells did not adopt dopaminergic cell fates in situ, consistent with the limited ability of these cells to undergo terminal differentiation into electrically active neurons in vitro. Moreover, re-exposure of neurally-differentiated ADAS cells to serum-containing medium in vitro confirmed ADAS cell phenotypic instability (plasticity). Lastly, given that gene expression analyses of in vitro-expanded ADAS cells revealed that both naïve and differentiated ADAS cells express potent dopaminergic survival factors, ADAS transplants may have exerted neuroprotective effects by production of trophic factors at the lesion site. ADAS cells may be ideal for ex vivo gene transfer therapies in Parkinson's disease treatment.

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“…MSCs further offer the advantages of 1) being an easily obtainable source; 2) possessing the ability for expansion in vitro; 3) lacking a requirement for immunosuppressive therapy to prevent rejections; and 4) having a reduced risk of malignant transformation [70]. Of note, it has also been suggested that MSCs are able to differentiate into neuron-like [111,112] and glia-like [112,113] lineages, although some have questioned this ability [114].…”

Section: Bone Marrow-derived Hematopoietic Progenitor Stem Cellsmentioning

confidence: 99%

Recent Advances and the Future of Stem Cell Therapies in Amyotrophic Lateral Sclerosis

2015

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Amyotrophic lateral sclerosis is a progressive neurodegenerative disease of the motor neurons without a known cure. Based on the possibility of cellular neuroprotection and early preclinical results, stem cells have gained widespread enthusiasm as a potential treatment strategy. Preclinical models demonstrate a protective role of engrafted stem cells and provided the basis for human trials carried out using various types of stem cells, as well as a range of cell delivery methods. To date, no trial has demonstrated a clear therapeutic benefit; however, results remain encouraging and are the basis for ongoing studies. In addition, stem cell technology continues to improve, and induced pluripotent stem cells may offer additional therapeutic options in the future. Improved disease models and clinical trials will be essential in order to validate stem cells as a beneficial therapy.

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Neuro-glial differentiation of human bone marrow stem cells in vitro

Cited by 187 publications

References 56 publications

Introducing Transcription Factors to Multipotent Mesenchymal Stem Cells: Making Transdifferentiation Possible

Introducing Transcription Factors to Multipotent Mesenchymal Stem Cells: Making Transdifferentiation Possible

Autologous transplants of Adipose-Derived Adult Stromal (ADAS) cells afford dopaminergic neuroprotection in a model of Parkinson's disease

Recent Advances and the Future of Stem Cell Therapies in Amyotrophic Lateral Sclerosis

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