Human Adipose Tissue-Derived Stem Cells Differentiate to Neuronal-like Lineage Cells without Specific Induction

Radhakrishnan, Subathra; Trentz, O; Parthasarathy, Vinoth Kumar; Sellathamby, Shanmugapriya

doi:10.4172/2324-9293.1000131

Cited by 6 publications

(9 citation statements)

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“…At this point, it remains unknown if/how these cells interact with their local environment; however, it is not unreasonable to consider that HEF serves as a reservoir of cells for local tissue maintenance/regeneration as well as serving as a local immunomodulatory and cell signalling tissue, in keeping with the role of fat in other anatomical sites. Adipose tissue has been studied in great detail, and it is firmly established as a tissue with potent biological activity and capacity serving a number of local and systemic functions, not to mention its potential as a regenerative tissue source [5, 6, 8, 9, 19, 28, 29, 33, 38, 43, 44]. Scientifically and intraoperatively, epidural fat still receives little or no attention and is considered largely to be irrelevant clinically.…”

Section: Discussionmentioning

confidence: 99%

Isolation and Characterization of an Adult Stem Cell Population from Human Epidural Fat

Al-Jezani

Cho

Masson

et al. 2019

Stem Cells International

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Study Design. Isolation and characterization of human epidural fat (HEF) stem/progenitor cells. Objective. To identify a progenitor population within HEF and to determine if they meet the minimal criteria of a mesenchymal stem cell (MSC). Summary of Background Data. The biological function, if any, has yet to be determined for HEF. The presence of MSCs within HEF may indicate a regenerative potential within the HEF. Methods. HEF was isolated from 10 patients during elective spinal surgery. HEF cells were differentiated along osteo-, adipo-, and chondrogenic lineages, with differentiation analyzed via qPCR and histology. The cell surface receptor profile of HEF cells was examined by flow cytometry. HEF cells were also assayed through the collagen contraction assay. Prx1CreERT2GFP:R26RTdTomato MSC lineage-tracking mice were employed to identify EF MSCs in vivo. Results. HEF cell lines were obtained from all 10 patients in the study. Cells from 2/10 patients demonstrated full MSC potential, while cells from 6/10 patients demonstrated progenitor potential; 2/10 patients presented with cells that retained only adipogenic potential. HEF cells demonstrated MSC surface marker expression. All patient cell lines contracted collagen gels. A Prx1-positive population in mouse epidural fat that appeared to contribute to the dura of the spinal cord was observed in vivo. Conclusions. MSC and progenitor populations are present within HEF. MSCs were not identified in all patients examined in the current study. Furthermore, all patient lines demonstrated collagen contraction capacity, suggesting either a contaminating activated fibroblast population or HEF MSCs/progenitors also demonstrating a fibroblast-like phenotype. In vivo analysis suggests that these cell populations may contribute to the dura. Overall, these results suggest that cells within epidural fat may play a biological role within the local environment above providing a mechanical buffer.

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Section: Discussionmentioning

confidence: 99%

Isolation and Characterization of an Adult Stem Cell Population from Human Epidural Fat

Al-Jezani

Cho

Masson

et al. 2019

Stem Cells International

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“…Furthermore, while substantial experimental information has been generated on the in vitro neuronal differentiation of bone marrowderived mesenchymal stem cells (MSCs), very few studies have been conducted on the IFP-derived ADSCs [5]. Our team has previously reported the presence of embryonic stem cell markers in infrapatellar fat pad-derived stem cells, as well as the inherent differentiation potential of ADSCs towards neuronal lineage cells without any specific induction [2,6]. However, there remains no method for signalinduced neuronal differentiation of IFP derived -ADSCs with biomimetic stage-specific markers.…”

Section: Introductionmentioning

confidence: 99%

In vitro transdifferentiation of human adipose tissue-derived stem cells to neural lineage cells - a stage-specific incidence

Radhakrishnan

Trentz

Reddy³

et al. 2019

Adipocyte

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The present Study investigated the intrinsic ability of adipose tissue-derived stem cells (ADSCs) and their neural transdifferentiation in a stage-specific manner. Woodbury’s Chemical induction was implemented with modifications to achieve neural transdifferentiation. In Group I, ADSCs were preinduced with β-mercaptoethanol (β-ME) and later, with neural induction medium (NIM). In Group II, ADSCs were directly treated with NIM. In Group III, a DNA methyltransferase (DNMT) inhibitor 5-azacytidine was applied to understand whether transdifferentiation is controlled by epigenetic marks. Irrespective of the presence of (β-ME), the differentiation protocol resulted in glial-lineage cells. Group III produced poorly -differentiated neural cells with neuron-specific enolase positivity. A neuroprogenitor stage (NPC) was identified at d 11 after induction only in Group I. In other groups, this stage was not morphologically distinct. We explored the stage-specific incidence NPC, by alternatively treating them with basic fibroblast growth factor (bFGF), and antioxidants to validate if different signalling could cause varied outcomes (Group IV). They differentiated into neurons, as defined by cell polarity and expression of specific proteins. Meanwhile, neuroprogenitors exposed to NIM (Group I) produced glial-lineage cells. Further refinement and study of the occurrence and terminal differentiation of neuroprogenitors would identify a promising source for neural tissue replacement.

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“…At later passages, cells were long and thin, with two or more nerve fibers resembling dendrite and axonal outgrowths of neurons. In our previous study, a subset of IFPSCs was found to differentiate into neuronal lineage cells without any specific induction (6); thus, in the present study, the cells were analyzed for early neuronal markers at each passage. A steep increase in the expression of nestin was observed at P3.…”

Section: Discussionmentioning

confidence: 99%

Effect of passaging on the stemness of infrapatellar fat pad‑derived stem cells and potential role of nucleostemin as a prognostic marker of impaired stemness

Radhakrishnan¹,

Trentz

Martin³

et al. 2019

Mol Med Report

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Infrapatellar fat pad-derived stem cells (IFPSCs) are emerging as an alternative to adipose tissue-derived stem cells (ADSCs) from other sources. They are a reliable source of autologous stem cells obtained from medical waste that are suitable for use in cell-based therapy, tissue engineering and regenerative medicine. Such clinical applications require a vast number of high-quality IFPSCs. Unlike embryonic stem cells (ESCs), ADSCs and IFPSCs have limited population doubling capacity; however, in vitro expansion of primary IFPSCs through multiple passages (referred to as P) is a crucial step to acquire the desired population of cells. The present study investigated the effect of multiple passages on the stemness of IFPSCs during expansion and the possibility of predicting the loss of stemness using certain markers. IFPSCs were isolated from infrapatellar fat pad tissue resected during knee arthroplasty performed on aged patients (>65 years old). These cells from the stromal vascular fraction were serially passaged to at least to P7, and their stemness characteristics were examined at each passage. It was observed that IFPSCs maintained their spindle-shaped morphology, self-renewability and homogeneity at P2-4. Furthermore, immunostaining revealed that these cells expressed mesenchymal stem cell (CD166, CD90 and CD105) and ESC markers [Sox2, Nanog, Oct4 and nucleostemin (NS)], whereas the hematopoietic stem cell marker CD45 was absent. These cells were also able to differentiate into the three germ layer cell types, thus confirming their ability to generate clinical grade cells. The findings indicated that prolonged culture of IFPSCs (P>6) led to the loss of the stem cell proliferative marker NS, with an increased population doubling time and progression toward neuronal differentiation, acquiring a neurogenic phenotype. Additionally, IFPSCs demonstrated an inherent ability to secrete neurotrophic factors and express receptors for these factors, which is the cause of neuronal differentiation at later passages. Therefore, these findings validated NS as a prognostic indicator for impaired stemness and identified IFPSCs as a promising source for cell-based therapy, particularly for neurodegenerative diseases.

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Human Adipose Tissue-Derived Stem Cells Differentiate to Neuronal-like Lineage Cells without Specific Induction

Cited by 6 publications

References 0 publications

Isolation and Characterization of an Adult Stem Cell Population from Human Epidural Fat

Isolation and Characterization of an Adult Stem Cell Population from Human Epidural Fat

In vitro transdifferentiation of human adipose tissue-derived stem cells to neural lineage cells - a stage-specific incidence

Effect of passaging on the stemness of infrapatellar fat pad‑derived stem cells and potential role of nucleostemin as a prognostic marker of impaired stemness

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