Differentiation of human adult-derived stem cells towards a neural lineage involves a dedifferentiation event prior to differentiation to neural phenotypes

Bueno, Carlos; Martinez-Morga, Marta; García‐Bernal, David; Moraleda, José Marı́a

doi:10.1038/s41598-021-91566-9

Cited by 12 publications

(26 citation statements)

References 64 publications

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“…Therefore, it would be interesting to examine whether chromatin-containing bodies can move independently of the movement of the main nuclei or if they are a product of the main nuclei movement. In previous publications (Bueno et al, 2019; Bueno et al, 2021), we suggested that nuclear remodelling sequence might occur during neural transdifferentiation from hMSCs. Nevertheless, with new data, we have realised that this hypothesis was wrong because, among other factors, it seems that not all hBM-MSCs form lobed nuclei during neural transdifferentiation.…”

Section: Discussionmentioning

confidence: 68%

“…A standard immunocytochemical protocol was used as previously described (Bueno et al, 2013; Bueno et al, 2019; Bueno et al, 2021). Histone H2B-GFP transfected hBM- MSCs were plated onto collagen IV (Sigma-Aldrich) coated plastic or glass coverslips and maintained in neural induction media.…”

Section: Methodsmentioning

confidence: 99%

“…Cell fusion has been put forward to explain the presence of gene-marked binucleated Purkinje neurons after gene-marked bone marrow-derived cell transplantation (Kemp et al, 2014; Alvarez-Dolado et al, 2003). We recently reported that MSCs isolated from adult human tissues (hMSCs) can transdifferentiate into neural-like cells without passing through a mitotic stage and that they shrank dramatically and changed their morphology to that of neural-like cells through active neurite extensión (Bueno et al, 2019; Bueno et al, 2021). These findings demonstrated that the transdifferentiation of hMSCs towards a neural lineage involves a dedifferentiation event prior to re-differentiation to neural phenotypes, thus definitively confirming that the rapid acquisition of a neural-like morphology during hMSC transdifferentiation is via a transdifferentiation trait rather than merely an artefact.…”

Section: Introductionmentioning

confidence: 99%

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Binucleated cells generated by nuclear movement during neural transdifferentiation from human bone marrow-derived mesenchymal cells

Bueno

Blanquer

García‐Bernal

et al. 2022

Preprint

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SummaryAlthough it has been reported that bone marrow-derived mesenchymal stromal cells (BM-MSCs) can transdifferentiate into neural cells, the findings are considered unlikely. Cell changes induced by cytotoxicity and cell fusion events are alternative explanations for these observations in culture and transplantation studies, respectively. Here, we showed that BM-MSC neural transdifferentiation involves the formation of dedifferentiated cells which can then redifferentiate into neural-like cells, redifferentiate back to the mesenchymal fate or even repeatedly switch lineages without cell division. Furthermore, we have discovered that nuclei from dedifferentiated cells rapidly move within the cell, adopting different morphologies and even forming binucleated cells. We also noted that dedifferentiated cells position their nucleus at the front of the cell during migration. Our results demonstrated that BM-MSCs can rapidly transdifferentiate into neural-like cells and binucleated BM-MSCs can form with independence of any cell fusion events, suggesting that BM-MSC neural transdifferentiation is a fact, not an artifact.HighlightshBM-MSC neural transdifferentiation involves the formation of dedifferentiated cells.hBM-MSCs could rapidly and repeatedly switch lineages without cell division.Nuclei from hBM-MSCs rapidly move within the cell adopting different morphologies.Binucleated hBM-MSCs can be formed with independence of any cell fusion events.

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Section: Discussionmentioning

confidence: 68%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Binucleated cells generated by nuclear movement during neural transdifferentiation from human bone marrow-derived mesenchymal cells

Bueno

Blanquer

García‐Bernal

et al. 2022

Preprint

Self Cite

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“…Time-lapse microscopy was used to examine the order of biological cascades during neural differentiation processes of hPDLSCs, human bone marrow mesenchymal stem cells (hBMSCs) and hDPSCs. It was demonstrated that these cells shrink substantially and via extension of neurites they change their shape to neuron-like cells; the important point is that a dedifferentiation stage occurs prior to differentiation into neural phenotypes [ 48 ].…”

Section: Periodontal Ligament-derived Mscsmentioning

confidence: 99%

Periodontal ligament stem cells as a promising therapeutic target for neural damage

et al. 2022

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Background The damaged neuronal cells of adult mammalian lack the regenerative ability to replace the neuronal connections. Periodontal ligament stem cells (PDLSCs) are the promising source for neuroregenerative applications that can improve the injured microenvironment of the damaged neural system. They provide neuronal progenitors and neurotrophic, anti-apoptotic and anti-inflammatory factors. In this study, we aimed to comprehensively explore the various neuronal differentiation potentials of PDLSCs for application in neural regeneration therapy. Main text PDLSCs have superior potential to differentiate into various neural-like cells through a dedifferentiation stage followed by differentiation process without need for cell division. Diverse combination of nutritional factors can be used to induce the PDLSCs toward neural lineage. PDLSCs when coupled with biomaterials could have significant implications for neural tissue repair. PDLSCs can be a new clinical research target for Alzheimer's disease treatment, multiple sclerosis and cerebral ischemia. Moreover, PDLSCs have beneficial effects on retinal ganglion cell regeneration and photoreceptor survival. PDLSCs can be a great source for the repair of injured peripheral nerve through the expression of several neural growth factors and differentiation into Schwann cells. Conclusion In conclusion, these cells are an appealing source for utilizing in clinical treatment of the neuropathological disorders. Although significant in vitro and in vivo investigations were carried out in order for neural differentiation evaluation of these cells into diverse types of neurons, more preclinical and clinical studies are needed to elucidate their therapeutic potential for neural diseases.

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“…MSCs can give rise to derivatives of both ectodermal and mesodermal lineages. For example, MSCs derived from dental ligament can easily be differentiated into neurons and cardiomyocytes, opening up possibilites in treatment of neuromuscular diseases by tackling different aspects of such a complex pathophysiology [ 85 , 86 , 87 , 88 , 89 ].…”

Section: Sources Of Cells For Transplantation Into Nervous and Heart Tissuementioning

confidence: 99%

Regenerative Neurology and Regenerative Cardiology: Shared Hurdles and Achievements

Mitrečić

Hribljan

Jagečić

et al. 2022

IJMS

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From the first success in cultivation of cells in vitro, it became clear that developing cell and/or tissue specific cultures would open a myriad of new opportunities for medical research. Expertise in various in vitro models has been developing over decades, so nowadays we benefit from highly specific in vitro systems imitating every organ of the human body. Moreover, obtaining sufficient number of standardized cells allows for cell transplantation approach with the goal of improving the regeneration of injured/disease affected tissue. However, different cell types bring different needs and place various types of hurdles on the path of regenerative neurology and regenerative cardiology. In this review, written by European experts gathered in Cost European action dedicated to neurology and cardiology-Bioneca, we present the experience acquired by working on two rather different organs: the brain and the heart. When taken into account that diseases of these two organs, mostly ischemic in their nature (stroke and heart infarction), bring by far the largest burden of the medical systems around Europe, it is not surprising that in vitro models of nervous and heart muscle tissue were in the focus of biomedical research in the last decades. In this review we describe and discuss hurdles which still impair further progress of regenerative neurology and cardiology and we detect those ones which are common to both fields and some, which are field-specific. With the goal to elucidate strategies which might be shared between regenerative neurology and cardiology we discuss methodological solutions which can help each of the fields to accelerate their development.

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Differentiation of human adult-derived stem cells towards a neural lineage involves a dedifferentiation event prior to differentiation to neural phenotypes

Cited by 12 publications

References 64 publications

Binucleated cells generated by nuclear movement during neural transdifferentiation from human bone marrow-derived mesenchymal cells

Binucleated cells generated by nuclear movement during neural transdifferentiation from human bone marrow-derived mesenchymal cells

Periodontal ligament stem cells as a promising therapeutic target for neural damage

Regenerative Neurology and Regenerative Cardiology: Shared Hurdles and Achievements

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