Differentiation of Mesenchymal Stem Cells to Neuroglia: in the Context of Cell Signalling

George, Sajan D.; Hamblin, Michael R.; Abrahamse, Heidi

doi:10.1007/s12015-019-09917-z

Cited by 73 publications

(45 citation statements)

References 159 publications

(180 reference statements)

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“…Adipose tissue is an abundant source of MSCs, and AT-MSCs can differentiate toward adipogenic, chondrogenic, and osteogenic cell lineages. Recent studies showed that AT-MSCs have the potential to differentiate into nonmesodermal cells such as neural cells, hepatocytes, and pancreatic beta cells [ 20 – 24 ]. Therefore, new strategies for the treatment of DM using AT-MSCs that differentiated into IPCs have been actively researched [ 25 , 26 ].…”

Section: Discussionmentioning

confidence: 99%

Generation of Insulin-Producing Cells from Canine Adipose Tissue-Derived Mesenchymal Stem Cells

Teshima

Okamoto

Dairaku

et al. 2020

Stem Cells International

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The potential of mesenchymal stem cells (MSCs) to differentiate into nonmesodermal cells such as pancreatic beta cells has been reported. New cell-based therapy using MSCs for diabetes mellitus is anticipated as an alternative treatment option to insulin injection or islet transplantation in both human and veterinary medicine. Several protocols were reported for differentiation of MSCs into insulin-producing cells (IPCs), but no studies have reported IPCs generated from canine MSCs. The purpose of this study was to generate IPCs from canine adipose tissue-derived MSCs (AT-MSCs) in vitro and to investigate the effects of IPC transplantation on diabetic mice in vivo. Culturing AT-MSCs with the differentiation protocol under a two-dimensional culture system did not produce IPCs. However, spheroid-like small clusters consisting of canine AT-MSCs and human recombinant peptide μ-pieces developed under a three-dimensional (3D) culture system were successfully differentiated into IPCs. The generated IPCs under 3D culture condition were stained with dithizone and anti-insulin antibody. Canine IPCs also showed gene expression typical for pancreatic beta cells and increased insulin secretion in response to glucose stimulation. The blood glucose levels in streptozotocin-induced diabetic mice were decreased after injection with the supernatant of canine IPCs, but the hyperglycemic states of diabetic mice were not improved after transplanting IPCs subcutaneously or intramesenterically. The histological examination showed that the transplanted small clusters of IPCs were successfully engrafted to the mice and included cells positive for insulin by immunofluorescence. Several factors, such as the transplanted cell number, the origin of AT-MSCs, and the differentiation protocol, were considered potential reasons for the inability to improve the hyperglycemic state after IPC transplantation. These findings suggest that canine AT-MSCs can be differentiated into IPCs under a 3D culture system and IPC transplantation may be a new treatment option for dogs with diabetes mellitus.

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Section: Discussionmentioning

confidence: 99%

Generation of Insulin-Producing Cells from Canine Adipose Tissue-Derived Mesenchymal Stem Cells

Teshima

Okamoto

Dairaku

et al. 2020

Stem Cells International

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“…Alternatively, differentiation of neurons from MSCs was reported in different ways such as using co-culture conditions, exosomes and graphene substrates [13][14][15]. Neuronal differentiation attempts of MSCs in media containing chemical reagents provided a faster differentiation rate compared to other methods [16]. The most accaptable identifiers of neuronal differentiation are morphological changes and neuronal gene expression profiles.…”

Section: Introductionmentioning

confidence: 99%

Neurons from human mesenchymal stem cells display both spontaneous and stimuli responsive activity

et al. 2020

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Mesenchymal stem cells have the ability to transdifferentiate into neurons and therefore one of the potential adult stem cell source for neuronal tissue regeneration applications and understanding neurodevelopmental processes. In many studies on human mesenchymal stem cell (hMSC) derived neurons, success in neuronal differentiation was limited to neuronal protein expressions which is not statisfactory in terms of neuronal activity. Established neuronal networks seen in culture have to be investigated in terms of synaptic signal transmission ability to develop a culture model for human neurons and further studying the mechanism of neuronal differentiation and neurological pathologies. Accordingly, in this study, we analysed the functionality of bone marrow hMSCs differentiated into neurons by a single step cytokine-based induction protocol. Neurons from both primary hMSCs and hMSC cell line displayed spontaneous activity (�75%) as demonstrated by Ca ++ imaging. Furthermore, when electrically stimulated, hMSC derived neurons (hMd-Neurons) matched the response of a typical neuron in the process of maturation. Our results reveal that a combination of neuronal inducers enhance differentiation capacity of bone marrow hMSCs into high yielding functional neurons with spontaneous activity and mature into electrophysiologically active state. Conceptually, we suggest these functional hMd-Neurons to be used as a tool for disease modelling of neuropathologies and neuronal differentiation studies.

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“…For in vitro differentiation of stem cells into neuronal precursors we used either commercially available ready-made neuronal medium with no fetal bovine serum, containing neuronal-specific GFs and penicillin/streptomycin, or have prepared a culture medium from Dulbecco's Modified Eagle's medium (DMEM) to which we added neuronal GFs BDNF, IGF-1, ascorbic acid and aminophylline, which is in line with established neuronal differentiation protocols ( 44 ). Fig.…”

Section: Treatmentmentioning

confidence: 99%

CD271+ stem cell treatment of patients with chronic stroke

Stancioiu¹,

Papadakis

Lazopoulos

et al. 2020

Exp Ther Med

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Patients with chronic stroke have currently little hope for motor improvement towards regaining independent activities of daily living; stem cell treatments offer a new treatment option and needs to be developed. Patients with chronic stroke (more than 3 months prior to stem cell treatment, mean 21.2 months post-stroke) were treated with CD271 + stem cells, 7 patients received autologous and 1 allogeneic cells from first degree relative; administration was intravenous in 1 and intrathecal in 7 patients. Each patient received a single treatment consisting of 2-5x10 6 cells/kg and they were followed up for up to 12 months. There were significant improvements in expressive aphasia (2/3 patients) spasticity (5/5, of which 2 were transient), and small improvements in motor function (2/8 patients). Although motor improvements were minor in our chronic stroke patients, improvements in aphasia and spasticity were significant and in the context of good safety we are advocating further administration and clinical studies of CD271 + stem cells not only in chronic stroke patients, but also for spastic paresis/plegia; a different, yet unexplored application is pulmonary emphysema.

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Differentiation of Mesenchymal Stem Cells to Neuroglia: in the Context of Cell Signalling

Cited by 73 publications

References 159 publications

Generation of Insulin-Producing Cells from Canine Adipose Tissue-Derived Mesenchymal Stem Cells

Generation of Insulin-Producing Cells from Canine Adipose Tissue-Derived Mesenchymal Stem Cells

Neurons from human mesenchymal stem cells display both spontaneous and stimuli responsive activity

CD271+ stem cell treatment of patients with chronic stroke

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