Dual Inhibition of Activin/Nodal/TGF-βand BMP Signaling Pathways by SB431542 and Dorsomorphin Induces Neuronal Differentiation of Human Adipose Derived Stem Cells

Damage to the nervous system can cause devastating diseases or musculoskeletal dysfunctions and transplantation of progenitor stem cells can be an excellent treatment option in this regard. Preclinical studies demonstrate that untreated stem cells, unlike stem cells activated to differentiate into neuronal lineage, do not survive in the neuronal tissues. Conventional methods of inducing neuronal differentiation of stem cells are complex and expensive. We therefore sought to determine if a simple, one-step, and cost effective method, previously reported to induce neuronal differentiation of embryonic stem cells and induced-pluripotent stem cells, can be applied to adult stem cells. Indeed, dual inhibition of activin/nodal/TGF-βand BMP pathways using SB431542 and dorsomorphin, respectively, induced neuronal differentiation of human adipose derived stem cells (hADSCs) as evidenced by formation of neurite extensions, protein expression of neuron-specific gamma enolase, and mRNA expression of neuron-specific transcription factors Sox1 and Pax6 and matured neuronal marker NF200. This process correlated with enhanced phosphorylation of p38, Erk1/2, PI3K, and Akt1/3. Additionally,in vitrosubcutaneous implants of SB431542 and dorsomorphin treated hADSCs displayed significantly higher expression of active-axonal-growth-specific marker GAP43. Our data offers novel insights into cell-based therapies for the nervous system repair.

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Application of Nanomaterials in Regulating the Fate of Adipose-derived Stem Cells

Current Stem Cell Research & Therapy ◽

10.2174/1574888x15666200502000343 ◽

2021 ◽

Vol 16 (1) ◽

pp. 3-13

Author(s):

Lang Wang ◽

Yong Li ◽

Maorui Zhang ◽

Kui Huang ◽

Shuanglin Peng ◽

...

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Stem Cell Research ◽

Adult Stem Cells ◽

Adipose Derived Stem Cells ◽

Proliferation And Differentiation ◽

Recent Developments ◽

Good Biocompatibility ◽

Regulatory Effects ◽

New Treatment

Adipose-derived stem cells are adult stem cells which are easy to obtain and multi-potent. Stem-cell therapy has become a promising new treatment for many diseases, and plays an increasingly important role in the field of tissue repair, regeneration and reconstruction. The physicochemical properties of the extracellular microenvironment contribute to the regulation of the fate of stem cells. Nanomaterials have stable particle size, large specific surface area and good biocompatibility, which has led them being recognized as having broad application prospects in the field of biomedicine. In this paper, we review recent developments of nanomaterials in adipose-derived stem cell research. Taken together, the current literature indicates that nanomaterials can regulate the proliferation and differentiation of adipose-derived stem cells. However, the properties and regulatory effects of nanomaterials can vary widely depending on their composition. This review aims to provide a comprehensive guide for future stem-cell research on the use of nanomaterials.

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Epigenetic Regulation of Mesenchymal Stem Cells: A Focus on Osteogenic and Adipogenic Differentiation

Stem Cells International ◽

10.4061/2011/201371 ◽

2011 ◽

Vol 2011 ◽

pp. 1-18 ◽

Cited By ~ 57

Author(s):

Chad M. Teven ◽

Xing Liu ◽

Ning Hu ◽

Ni Tang ◽

Stephanie H. Kim ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Epigenetic Regulation ◽

Adult Stem Cells ◽

Es Cells ◽

Adipogenic Differentiation ◽

Embryonic Stem ◽

Cell Types ◽

Differentiation Potential ◽

Msc Differentiation

Stem cells are characterized by their capability to self-renew and terminally differentiate into multiple cell types. Somatic or adult stem cells have a finite self-renewal capacity and are lineage-restricted. The use of adult stem cells for therapeutic purposes has been a topic of recent interest given the ethical considerations associated with embryonic stem (ES) cells. Mesenchymal stem cells (MSCs) are adult stem cells that can differentiate into osteogenic, adipogenic, chondrogenic, or myogenic lineages. Owing to their ease of isolation and unique characteristics, MSCs have been widely regarded as potential candidates for tissue engineering and repair. While various signaling molecules important to MSC differentiation have been identified, our complete understanding of this process is lacking. Recent investigations focused on the role of epigenetic regulation in lineage-specific differentiation of MSCs have shown that unique patterns of DNA methylation and histone modifications play an important role in the induction of MSC differentiation toward specific lineages. Nevertheless, MSC epigenetic profiles reflect a more restricted differentiation potential as compared to ES cells. Here we review the effect of epigenetic modifications on MSC multipotency and differentiation, with a focus on osteogenic and adipogenic differentiation. We also highlight clinical applications of MSC epigenetics and nuclear reprogramming.

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Impact of the Epigenetically Regulated Hoxa-5 Gene in Neural Differentiation from Human Adipose-Derived Stem Cells

Biology ◽

10.3390/biology10080802 ◽

2021 ◽

Vol 10 (8) ◽

pp. 802

Author(s):

Rosa Hernández ◽

Cristina Jiménez-Luna ◽

Raúl Ortiz ◽

Fernando Setién ◽

Miguel López ◽

...

Keyword(s):

Stem Cells ◽

Neuronal Differentiation ◽

Essential Gene ◽

Deep Understanding ◽

Potential Candidate ◽

Epigenetic Changes ◽

Neuronal Marker ◽

Functional Studies ◽

Culture Cells ◽

Important Barrier

Human adipose-derived mesenchymal stem cells (hASCs) may be used in some nervous system pathologies, although obtaining an adequate degree of neuronal differentiation is an important barrier to their applicability. This requires a deep understanding of the expression and epigenetic changes of the most important genes involved in their differentiation. We used hASCs from human lipoaspirates to induce neuronal-like cells through three protocols (Neu1, 2, and 3), determined the degree of neuronal differentiation using specific biomarkers in culture cells and neurospheres, and analyzed epigenetic changes of genes involved in this differentiation. Furthermore, we selected the Hoxa-5 gene to determine its potential to improve neuronal differentiation. Our results showed that an excellent hASC neuronal differentiation process using Neu1 which efficiently modulated NES, CHAT, SNAP25, or SCN9A neuronal marker expression. In addition, epigenetic studies showed relevant changes in Hoxa-5, GRM4, FGFR1, RTEL1, METRN, and PAX9 genes. Functional studies of the Hoxa-5 gene using CRISPR/dCas9 and lentiviral systems showed that its overexpression induced hASCs neuronal differentiation that was accelerated with the exposure to Neu1. These results suggest that Hoxa-5 is an essential gene in hASCs neuronal differentiation and therefore, a potential candidate for the development of cell therapy strategies in neurological disorders.

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Co-transplantation of autologous adult stem cells together with differentiated derivatives of human embryonic stem cells. A novel strategy to enhance the efficacy of autologous cell-transplantation therapy?

Wound Repair and Regeneration ◽

10.1111/j.1067-1927.2005.130320.x ◽

2005 ◽

Vol 13 (3) ◽

pp. 353-356

Author(s):

Boon Chin Heng ◽

Tong Cao

Keyword(s):

Stem Cells ◽

Human Embryonic Stem Cells ◽

Adult Stem Cells ◽

Embryonic Stem ◽

Autologous Cell ◽

Novel Strategy ◽

Autologous Cell Transplantation ◽

Derivatives Of ◽

Cell Transplantation Therapy ◽

Transplantation Therapy

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Types of Stem Cells Used in US-Based Clinical Trials between 1999 and 2014

Catholic Social Science Review ◽

10.5840/cssr20212635 ◽

2021 ◽

Vol 26 ◽

pp. 169-191

Author(s):

Emma E. Redfield ◽

Erin K. Luciano ◽

Monica J. Sewell ◽

Lucas A. Mitzel ◽

Isaac J. Sanford ◽

...

Keyword(s):

Stem Cells ◽

Clinical Trials ◽

Stem Cell ◽

Embryonic Stem Cells ◽

Adult Stem Cells ◽

Embryonic Stem ◽

Cell Types ◽

The Us ◽

Health Database ◽

Induced Pluripotent

This study looks at the number of clinical trials involving specific stem cell types. To our knowledge, this has never been done before. Stem cell clinical trials that were conducted at locations in the US and registered on the National Institutes of Health database at ‘clinicaltrials.gov’ were categorized according to the type of stem cell used (adult, cancer, embryonic, perinatal, or induced pluripotent) and the year that the trial was registered. From 1999 to 2014, there were 2,357 US stem cell clinical trials registered on ‘clinicaltrials.gov,’ and 89 percent were from adult stem cells and only 0.12 percent were from embryonic stem cells. This study concludes that embryonic stem cells should no longer be used for clinical study because of their irrelevance, moral questions, and induced pluripotent stem cells.

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Dermatan sulphate promotes neuronal differentiation in mouse and human stem cells

The Journal of Biochemistry ◽

10.1093/jb/mvaa087 ◽

2020 ◽

Cited By ~ 1

Author(s):

Chika Ogura ◽

Kazumi Hirano ◽

Shuji Mizumoto ◽

Shuhei Yamada ◽

Shoko Nishihara

Keyword(s):

Stem Cells ◽

Neurite Outgrowth ◽

Neuronal Differentiation ◽

Neural Progenitor Cells ◽

Chondroitin Sulphate ◽

Heparan Sulphate ◽

Embryonic Stem ◽

Hydroxyl Group ◽

Human Stem Cells ◽

Dermatan Sulphate

Abstract Dermatan sulphate (DS), a glycosaminoglycan, is present in the extracellular matrix and on the cell surface. Previously, we showed that heparan sulphate plays a key role in the maintenance of the undifferentiated state in mouse embryonic stem cells (mESCs) and in the regulation of their differentiation. Chondroitin sulphate has also been to be important for pluripotency and differentiation of mESCs. Keratan sulphate is a marker of human pluripotent stem cells. To date, however, the function of DS in mESCs has not been clarified. Dermatan 4 sulfotransferase 1, which transfers sulphate to the C-4 hydroxyl group of N-acetylgalactosamine of DS, contributes to neuronal differentiation of mouse neural progenitor cells. Therefore, we anticipated that neuronal differentiation would be induced in mESCs in culture by the addition of DS. To test this expectation, we investigated neuronal differentiation in mESCs and human neural stem cells (hNSCs) cultures containing DS. In mESCs, DS promoted neuronal differentiation by activation of extracellular signal-regulated kinase 1/2 and also accelerated neurite outgrowth. In hNSCs, DS promoted neuronal differentiation and neuronal migration, but not neurite outgrowth. Thus, DS promotes neuronal differentiation in both mouse and human stem cells, suggesting that it offers a novel method for efficiently inducing neuronal differentiation.

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Cardiac Regeneration After Myocardial Infarction: an Approachable Goal

Current Cardiology Reports ◽

10.1007/s11886-020-01361-7 ◽

2020 ◽

Vol 22 (10) ◽

Author(s):

Mauro Giacca

Keyword(s):

Myocardial Infarction ◽

Stem Cells ◽

Pluripotent Stem Cells ◽

Adult Stem Cells ◽

Ex Vivo ◽

Embryonic Stem ◽

Cardiac Regeneration ◽

Myocardial Tissue ◽

Induced Pluripotent ◽

Large Animals

Abstract Purpose of Review Until recently, cardiac regeneration after myocardial infarction has remained a holy grail in cardiology. Failure of clinical trials using adult stem cells and scepticism about the actual existence of such cells has reinforced the notion that the heart is an irreversibly post-mitotic organ. Recent evidence has drastically challenged this conclusion. Recent Findings Cardiac regeneration can successfully be obtained by at least two strategies. First, new cardiomyocytes can be generated from embryonic stem cells or induced pluripotent stem cells and administered to the heart either as cell suspensions or upon ex vivo generation of contractile myocardial tissue. Alternatively, the endogenous capacity of cardiomyocytes to proliferate can be stimulated by the delivery of individual genes or, more successfully, of selected microRNAs. Summary Recent experimental success in large animals by both strategies now fuels the notion that cardiac regeneration is indeed possible. Several technical hurdles, however, still need to be addressed and solved before broad and successful clinical application is achieved.

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HMGA Proteins in Stemness and Differentiation of Embryonic and Adult Stem Cells

International Journal of Molecular Sciences ◽

10.3390/ijms21010362 ◽

2020 ◽

Vol 21 (1) ◽

pp. 362 ◽

Cited By ~ 9

Author(s):

Silvia Parisi ◽

Silvia Piscitelli ◽

Fabiana Passaro ◽

Tommaso Russo

Keyword(s):

Experimental Data ◽

Stem Cells ◽

Cell Fate ◽

Adult Stem Cells ◽

Regulation Of Gene Expression ◽

Embryonic Stem ◽

Adult Stem Cell ◽

Mouse Development ◽

Architectural Proteins ◽

Numerous Experimental Data

HMGA1 and HMGA2 are chromatin architectural proteins that do not have transcriptional activity per se, but are able to modify chromatin structure by interacting with the transcriptional machinery and thus negatively or positively regulate the transcription of several genes. They have been extensively studied in cancer where they are often found to be overexpressed but their functions under physiologic conditions have still not been completely addressed. Hmga1 and Hmga2 are expressed during the early stages of mouse development, whereas they are not detectable in most adult tissues. Hmga overexpression or knockout studies in mouse have pointed to a key function in the development of the embryo and of various tissues. HMGA proteins are expressed in embryonic stem cells and in some adult stem cells and numerous experimental data have indicated that they play a fundamental role in the maintenance of stemness and in the regulation of differentiation. In this review, we discuss available experimental data on HMGA1 and HMGA2 functions in governing embryonic and adult stem cell fate. Moreover, based on the available evidence, we will aim to outline how HMGA expression is regulated in different contexts and how these two proteins contribute to the regulation of gene expression and chromatin architecture in stem cells.

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Regulation of Prostatic Stem Cells by Stromal Niche in Health and Disease

Endocrinology ◽

10.1210/en.2008-0465 ◽

2008 ◽

Vol 149 (9) ◽

pp. 4303-4306 ◽

Cited By ~ 18

Author(s):

Gail P. Risbridger ◽

Renea A. Taylor

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Adult Stem Cells ◽

Embryonic Stem ◽

Tumor Stroma ◽

Stem Cell Differentiation ◽

Stem Cell Regulation ◽

Isolation And Characterization ◽

Tissue Recombination ◽

Cell Niche

The isolation and characterization of prostatic stem cells has received significant attention in the last few years based on the belief that aberrant regulation of adult stem cells leads to prostate disease including cancer. The nature of the perturbations in stem cell regulation remains largely unknown. Although adult stem cells are can be governed by autonomous regulatory mechanisms, the stromal niche environment also provides essential cues to direct directing differentiation decisions and can lead to aberrant proliferation and/or differentiation. Elegant tissue recombination experiments, pioneered by Gerald Cunha and colleagues, provided evidence that quiescent epithelial tissues containing adult stem cells were capable of altered differentiation in response to inductive and instructive mesenchyme. In more recent times, it has been demonstrated that embryonic mesenchyme is sufficiently powerful to direct the differentiation of embryonic stem cells into mature prostate or bladder. In addition, prostatic tumor stroma provides another unique niche or microenvironment for stem cell differentiation that is distinct to normal stroma. This review highlights the importance of the appropriate selection of the stromal cell niche for tissue regeneration and implies plasticity of adult stem cells that is dictated by the tissue microenvironment.

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