Stem Cell Regenerative Medicine Research Articles

Stem cells in regenerative medicine-from bench to bedside

The use of mesenchymal stem cells for regenerative medicine is becoming more popular than ever before-even though their clinical usage is limited. Many ethical and translational questions, as well as legal aspects and uncertainty regarding safety inhibit the growth of appropriate therapies from promising scientific approaches.This paper demonstrates the main problems of the translation from stem cell based therapies from basic science towards their clinical use.

Current Status and Future Prospects of Genome-Scale Metabolic Modeling to Optimize the Use of Mesenchymal Stem Cells in Regenerative Medicine.

Mesenchymal stem cells are a promising source for externally grown tissue replacements and patient-specific immunomodulatory treatments. This promise has not yet been fulfilled in part due to production scaling issues and the need to maintain the correct phenotype after re-implantation. One aspect of extracorporeal growth that may be manipulated to optimize cell growth and differentiation is metabolism. The metabolism of MSCs changes during and in response to differentiation and immunomodulatory changes. MSC metabolism may be linked to functional differences but how this occurs and influences MSC function remains unclear. Understanding how MSC metabolism relates to cell function is however important as metabolite availability and environmental circumstances in the body may affect the success of implantation. Genome-scale constraint based metabolic modeling can be used as a tool to fill gaps in knowledge of MSC metabolism, acting as a framework to integrate and understand various data types (e.g., genomic, transcriptomic and metabolomic). These approaches have long been used to optimize the growth and productivity of bacterial production systems and are being increasingly used to provide insights into human health research. Production of tissue for implantation using MSCs requires both optimized production of cell mass and the understanding of the patient and phenotype specific metabolic situation. This review considers the current knowledge of MSC metabolism and how it may be optimized along with the current and future uses of genome scale constraint based metabolic modeling to further this aim.

Lessons Learned from Somatic Cell Nuclear Transfer.

Somatic cell nuclear transfer (SCNT) has been an area of interest in the field of stem cell research and regenerative medicine for the past 20 years. The main biological goal of SCNT is to reverse the differentiated state of a somatic cell, for the purpose of creating blastocysts from which embryonic stem cells (ESCs) can be derived for therapeutic cloning, or for the purpose of reproductive cloning. However, the consensus is that the low efficiency in creating normal viable offspring in animals by SCNT (1–5%) and the high number of abnormalities seen in these cloned animals is due to epigenetic reprogramming failure. In this review we provide an overview of the current literature on SCNT, focusing on protocol development, which includes early SCNT protocol deficiencies and optimizations along with donor cell type and cell cycle synchrony; epigenetic reprogramming in SCNT; current protocol optimizations such as nuclear reprogramming strategies that can be applied to improve epigenetic reprogramming by SCNT; applications of SCNT; the ethical and legal implications of SCNT in humans; and specific lessons learned for establishing an optimized SCNT protocol using a mouse model.

Industry Updates from the Field of Stem Cell Research and Regenerative Medicine in January 2020: Industry News

Latest developments in the field of stem cell research and regenerative medicine compiled from publicly available information and press releases from nonacademic institutions in January 2020.

Yes-Associated Protein and PDZ Binding Motif: A Critical Signaling Pathway in the Control of Human Pluripotent Stem Cells Self-Renewal and Differentiation

Human pluripotent stem cells (hPSCs) can self-renew indefinitely to generate cells like themselves with a normal karyotype and differentiate into other types of cells when stimulated with a proper set of internal and external signals. hPSCs including human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs) are an alternative approach toward stem cell biology, drug discovery, disease modeling, and regenerative medicine. hESCs are commonly derived from the inner cell mass of preimplantation embryos and can maintain their pluripotency in appropriate culture media. The Hippo pathway is a major integrator of cell surface-mediated signals and plays an essential role in regulating hESCs function. Yes-associated protein (YAP) and TAZ (PDZ binding motif) are critical downstream transcriptional coactivators in the Hippo pathway. The culture conditions have effects on the cytoplasmic or nuclear YAP/TAZ localization. Also, the activity of Hippo pathway is influenced by cell density, mechanical tension, and biochemical signals. In this review article, we summarize the function of YAP/TAZ and focus on the regulation of YAP/TAZ in self-renewal and differentiation of hESCs.

Cryo-imaging of Stem Cell Biodistribution in Mouse Model of Graft-Versus-Host-Disease.

We demonstrated the use of multispectral cryo-imaging and software to analyze human mesenchymal stromal cells (hMSCs) biodistribution in mouse models of graft-versus-host-disease (GVHD) following allogeneic bone marrow transplantation (BMT). We injected quantum dot labeled MSCs via tail vein to mice receiving BMT and analyzed hMSC biodistribution in major organs (e.g. lung, liver, spleen, kidneys and bone marrow). We compared the biodistribution of hMSCs in mice following allogeneic BMT recipients (with GVHD) to the biodistribution following syngeneic BMT (without GVHD). Cryo-imaging system revealed cellular biodistribution and redistribution patterns in the animal model. We initially found clusters of cells in the lung that eventually dissociated to single cells and redistributed to other organs within 72h. The in vivo half-life of the exogenous MSCs was about 21h. We found that the biodistribution of stromal cells was not related to blood flow, rather cells preferentially homed to specific organs. In conclusion, cryo-imaging was suitable for analyzing the cellular biodistribution. It could provide capabilities of visualizing cells anywhere in the mouse model with single cell sensitivity. By characterizing the biodistribution and anatomical specificity of a therapeutic cellular product, we believe that cryo-imaging can play an important role in the advancement of stem and stromal cell therapies and regenerative medicine.

Industry Updates from the Field of Stem Cell Research and Regenerative Medicine in November 2019

Latest developments in the field of stem cell research and regenerative medicine compiled from publicly available information and press releases from nonacademic institutions in November 2019.

Industry Updates from the Field of Stem Cell Research and Regenerative Medicine in December 2019

Latest developments in the field of stem cell research and regenerative medicine compiled from publicly available information and press releases from nonacademic institutions in December 2019.

Industry Updates from the Field of Stem Cell Research and Regenerative Medicine in October 2019

Latest developments in the field of stem cell research and regenerative medicine compiled from publicly available information and press releases from nonacademic institutions in October 2019.

Cold Atmospheric Pressure Plasma as a Tool to Control the Proliferation of Various Mammalian Cells Including Human Mesenchymal Stem Cells for Regenerative Medicine

Cold Atmospheric Pressure Plasma as a Tool to Control the Proliferation of Various Mammalian Cells Including Human Mesenchymal Stem Cells for Regenerative Medicine

Genome-wide interaction target profiling reveals a novel Peblr20-eRNA activation pathway to control stem cell pluripotency.

Background: Long non-coding RNAs (lncRNAs) constitute an important component of the regulatory apparatus that controls stem cell pluripotency. However, the specific mechanisms utilized by these lncRNAs in the control of pluripotency are not fully characterized.Methods: We utilized a RNA reverse transcription-associated trap sequencing (RAT-seq) approach to profile the mouse genome-wide interaction targets for lncRNAs that are screened by RNA-seq.Results: We identified Peblr20 (Pou5F1 enhancer binding lncRNA 20) as a novel lncRNA that is associated with stem cell reprogramming. Peblr20 was differentially transcribed in fibroblasts compared to induced pluripotent stem cells (iPSCs). Notably, we found that Peblr20 utilized a trans mechanism to interact with the regulatory elements of multiple stemness genes. Using gain- and loss-of-function experiments, we showed that knockdown of Peblr20 caused iPSCs to exit from pluripotency, while overexpression of Peblr20 activated endogenous Pou5F1 expression. We further showed that Peblr20 promoted pluripotent reprogramming. Mechanistically, we demonstrated that Peblr20 activated endogenous Pou5F1 by binding to the Pou5F1 enhancer in trans, recruiting TET2 demethylase and activating the enhancer-transcribed RNAs.Conclusions: Our data reveal a novel epigenetic mechanism by which a lncRNA controls the fate of stem cells by trans-regulating the Pou5F1 enhancer RNA pathway. We demonstrate the potential for leveraging lncRNA biology to enhance the generation of stem cells for regenerative medicine.

Epidermal Stem Cells in Regenerative Medicine.

Stem cells present in the epidermis, and hair follicle, guarantee the conservation of adult skin maintenance and hair renewal, but they also play a pivotal role in wound repair and tissue regeneration. Adult stem cells present in the epidermis are also responsible for epidermis different layers' regeneration.We here summarize the epidermal stem cells information in term of their central features in stem cells niche, their signalling pathways and their maintenance, and activation.

Stem Cell Aging and Regenerative Medicine.

Stem cells are a promising source for regenerative medicine to cure a plethora of diseases that are currently treated based on either palliative or symptomatic relief or by preventing their onset and progression. Aging-associated degenerative changes in stem cells, stem cell niches, and signaling pathways bring a step by step decline in the regenerative and functional potential of tissues. Clinical studies and experiments on model organisms have pointed out checkpoints that aging will inevitably impose on stem cell aiming for transplantation and hence questions are raised about the age of the donor. In the following discourse, we review the fundamental molecular pathways that are implicated in stem cell aging and the current progress in tissue engineering and transplantation of each type of stem cells in regenerative medicine. We further focus on the consequences of stem cell aging on their clinical uses and the development of novel strategies to bypass those pitfalls and improve tissue replenishment.

Tissues from Post-Mortem Donors as Alternative Sources of Stem Cells for Regenerative Medicine.

Stem cells provide for all of the tissues in our body during embryogenesis. In adult organisms, they can be found as rare populations of tissue-specific stem cells in quiescent states, although they can still regenerate damaged tissues. Astonishingly, these cells are retained in tissues even post-mortem. There have been several reports that have provided evidence that cells with stem-like capabilities can be isolated, expanded, and differentiated in vitro from various tissues several hours, or even several days, post-mortem. Moreover, some post-mortem-tissue-derived stem cells can successfully engraft and regenerate injured host tissues. Here, we review in-vitro and in-vivo studies that provide evidence of isolation and characterization of stem cells from different tissues post-mortem, with a focus on the musculoskeletal and neural systems. Finally, we discuss their potential for use in regenerative medicine, and what needs to be done in further research toward their better exploitation.

18th Annual Meeting of the International Society for Stem Cell Research (ISSCR). Virtual Meeting - June 23-27, 2020

The Annual Meeting of the International Society for Stem Cell Research (ISSCR) brought together experts from across the world in the field of stem cell therapy research and regenerative medicine Due to the COVID-19 pandemic, the meeting, due to take place in Boston, was transformed into a virtual event, but still managed to achieve its aim of providing updates on all areas of stem cell science and regenerative medicine in oral and poster presentations provided online and on-demand to attendees This report covers some of the highlights from this virtual meeting

Interfacing human induced pluripotent stem cell-derived neurons with designed nanowire arrays as a future platform for medical applications.

Nanostructured substrates such as nanowire arrays form a powerful tool for building next-generation medical devices. So far, human pluripotent stem cell-derived neurons-a revolutionary tool for studying physiological function and modeling neurodegenerative diseases-have not been applied to such innovative substrates, due to the highly demanding nature of stem cell quality control and directed differentiation procedures to generate specialized cell types. Our study closes this gap, by presenting electrophysiologically mature human pluripotent stem cell-derived neurons on a set of nanowires in different patterns and growth densities after only four weeks of maturation-thereof 14 to 16 days on the nanowire arrays. While cell viability is maintained on all nanowire substrates, the settling regime of the cells can be controlled and tuned by the nanowire density from a fakir-like state to a complete nanowire wrapping state. Especially, full electrophysiological integrity of the neurons independent of the settling regime has been revealed by patch clamp experiments showing characteristic action potentials. Based on these results, our protocol has the potential to open new pathways in stem cell research and regenerative medicine utilizing human stem cell-derived neurons on tailor-made nanostructured substrates.

Stem Cell Research and Regenerative Medicine

Stem Cell Research and Regenerative Medicine

Peptidic Alginate-Based Hydrogels Demonstrate Chemotaxis and Expansion to Adipose Tissue Derived and Blood Derived Stem Cells

Biodegradable scaffolds have a major therapeutic advantage in regenerative medicine with their ability to include multiple compounds of drugs, growth factors and more recently, stem cells within the matrix. The scaffold can be programmed with mechanoresistive parameters targeted to the tissue to be replaced. Direct chemoattraction of in vivo stem cells to the implanted scaffold would be advantageous in the clinical setting. Large peptides such as vasculo-endothelial growth factor have demonstrated chemotaxis for angiogenesis from endothelial cells. This suggests other endogenous peptides may be present to directly attract stem cells to a scaffold. This exploratory study assessed if peptides from the blood peptidome would display chemotaxis to stem cells. Results showed that several short N-mer peptides demonstrated remarkable chemotaxis to blood and adipose tissue derived stem cells. Sodium alginate hydrogel was placed into 6-well, 24-well plate, and partitioned plates with channels between the wells. Connected wells were in series and spiked with peptides, biofluids containing stem cells and control wells. Images were recorded between three and nine days after incubation at 37°C. There were rapid migration and expansion of stem cells into the peptide wells. Cell analysis revealed activated stem cells on a number of parameters including autophagy, Ki67 and nitric oxide. Potentially, this enhanced method to bioscaffold design utilizing peptide chemoattraction could result in an improved approach for stem cell therapy and regenerative medicine applications. Specific patient groups (e.g. blood coagulation disorders) where surgery to acquire adipose tissue or bone marrow is contraindicated may benefit. In addition, the technology is portable and safe by using “on demand” peripheral blood derived stem cells and would be particularly suitable for specialized environments such as space medicine.

Stem cells for regenerative medicine and anti-aging

Stem cells for regenerative medicine and anti-aging

Evidence for existence of molecular stemness markers in porcine ovarian follicular granulosa cells

Abstract Granulosa cells (GCs) are important component of the follicle, a principal functional unit of the ovary. They undergo highly dynamic changes during folliculogenesis and play a vital role in oocyte’s maturation. Recently, it has been shown that GCs also exhibit stem cell properties, since they express OCT-4, Nanog, Sox-2, which are markers of pluripotency, as well as several mesenchymal stem cell markers, such as CD29, CD44, CD90, CD105, CD117 or CD166. In addition, GCs are able to differentiate towards neurogenic, chondrogenic and osteogenic lineages. Since the use of embryonic stem cells in regenerative medicine is burdened with ethical concerns and the risk of immune rejection or teratoma formation, adult stem cells are emerging as a promising alternative. GCs especially seem to provide a promising source of stem cells, since they are easily obtainable during assisted reproduction techniques. In order to better understand the genetic changes taking place in proliferating granulosa cells cultured in vitro, we isolated GCs from 40 prepubertal gilts and cultured them in vitro for 168 h. After 24, 48, 72, 96, 120, 144 and 168 h of cultivation the total RNA was extracted, reverse transcription was conducted and RT-qPCR reaction was performed. We observed that CD44, CD90 and IGF1 were upregulated after the cultivation, whereas CD105 and LIF were downregulated. Collectively, our results confirm stemness potential of porcine GCs and provide an insight into the transcriptome changes during in vitro cultivation. Running title: Molecular stemness markers in porcine granulosa cells