Stem cell therapy in multiple sclerosis: promise and controversy

2008 ◽  
Vol 14 (4) ◽  
pp. 541-546 ◽  
Author(s):  
ID Duncan ◽  
S Goldman ◽  
WB Macklin ◽  
M Rao ◽  
LP Weiner ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Stem Cells ◽  
Neurological Disease ◽  
Research Priorities ◽  
Current State ◽  
Stem And Progenitor Cells ◽  
National Multiple Sclerosis Society ◽  
Development In Vitro

Stem cells offer the potential for regeneration of lost tissue in neurological disease, including multiple sclerosis (MS). Their development in vitro and their use in vivo in animal models of degenerative neurological disease and recent first efforts in human clinical trials were the topics of a recent international meeting sponsored by the Multiple Sclerosis International Federation and the National Multiple Sclerosis Society on “Stem Cells & MS: Prospects and Strategies” Participants reviewed the current state of knowledge about the potential use of stem and progenitor cells in MS and other degenerative neurological disorders and outlined a series of urgent fundamental and applied clinical research priorities that should allow the potential of regeneration of damaged tissue in MS to be assessed and pursued.

Analysis of the hematopoietic potential of muscle-derived cells in mice

Blood ◽  
2002 ◽  
Vol 100 (2) ◽  
pp. 721-723 ◽  
Author(s):  
Hartmut Geiger ◽  
Jarrod M. True ◽  
Barry Grimes ◽  
Elizabeth J. Carroll ◽  
Roger A. Fleischman ◽  
...  
Keyword(s):  
Stem Cells ◽  
Muscle Tissue ◽  
Cell Sorting ◽  
Hematopoietic Stem ◽  
Hematopoietic System ◽  
Muscle Stem Cells ◽  
Antibody Staining ◽  
Stem And Progenitor Cells

Abstract Cells in murine muscle have been reported to differentiate into hematopoietic stem and progenitor cells and thus repopulate the hematopoietic system of an irradiated animal. This activity was attributed to muscle stem cells. We used an in vitro and in vivo approach to identify the hematopoietic repopulating activity found in muscle tissue of mice by antibody staining and cell sorting. We confirmed existence of a hematopoietic repopulating cell in muscle tissue, but the data strongly suggest that repopulation is due not to muscle stem cells but to hematopoietic cells present in muscle tissue. Unexpectedly, the blood-forming cells were enriched in muscle relative to their frequency in peripheral blood.

scholarly journals Loss of Ubiquitin Carboxy-Terminal Hydrolase L1 Impairs Long-Term Differentiation Competence and Metabolic Regulation in Murine Spermatogonial Stem Cells

Cells ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 2265
Author(s):  
Whitney F. Alpaugh ◽  
Anna L. Voigt ◽  
Rkia Dardari ◽  
Lin Su ◽  
Iman Al Khatib ◽  
...  
Keyword(s):  
Stem Cells ◽  
Metabolic Regulation ◽  
Spermatogonial Stem Cells ◽  
Seminiferous Tubules ◽  
Testis Weight ◽  
Stem And Progenitor Cells ◽  
Cell Transcriptome ◽  
Carboxy Terminal

Spermatogonia are stem and progenitor cells responsible for maintaining mammalian spermatogenesis. Preserving the balance between self-renewal of spermatogonial stem cells (SSCs) and differentiation is critical for spermatogenesis and fertility. Ubiquitin carboxy-terminal hydrolase-L1 (UCH-L1) is highly expressed in spermatogonia of many species; however, its functional role has not been identified. Here, we aimed to understand the role of UCH-L1 in murine spermatogonia using a Uch-l1−/− mouse model. We confirmed that UCH-L1 is expressed in undifferentiated and early-differentiating spermatogonia in the post-natal mammalian testis. The Uch-l1−/− mice showed reduced testis weight and progressive degeneration of seminiferous tubules. Single-cell transcriptome analysis detected a dysregulated metabolic profile in spermatogonia of Uch-l1−/− compared to wild-type mice. Furthermore, cultured Uch-l1−/− SSCs had decreased capacity in regenerating full spermatogenesis after transplantation in vivo and accelerated oxidative phosphorylation (OXPHOS) during maintenance in vitro. Together, these results indicate that the absence of UCH-L1 impacts the maintenance of SSC homeostasis and metabolism and impacts the differentiation competence. Metabolic perturbations associated with loss of UCH-L1 appear to underlie a reduced capacity for supporting spermatogenesis and fertility with age. This work is one step further in understanding the complex regulatory circuits underlying SSC function.

scholarly journals Chd1 regulates repair of promoter-proximal DNA breaks to sustain hypertranscription in embryonic stem cells

2019 ◽  
Author(s):  
Aydan Bulut-Karslioglu ◽  
Hu Jin ◽  
Marcela Guzman-Ayala ◽  
Andrew JK Williamson ◽  
Miroslav Hejna ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cancer Biology ◽  
Es Cells ◽  
Embryonic Stem ◽  
Dependent Manner ◽  
Dna Breaks ◽  
Pol I ◽  
Stem And Progenitor Cells

AbstractStem and progenitor cells undergo a global elevation of nascent transcription, or hypertranscription, during key developmental transitions involving rapid cell proliferation. The chromatin remodeler Chd1 binds to genes transcribed by RNA Polymerase (Pol) I and II and is required for hypertranscription in embryonic stem (ES) cells in vitro and the early post-implantation epiblast in vivo. Biochemically, Chd1 has been shown to facilitate transcription at least in part by removing nucleosomal barriers to elongation, but its mechanism of action in stem cells remains poorly understood. Here we report a novel role for Chd1 in the repair of promoter-proximal endogenous double-stranded DNA breaks (DSBs) in ES cells. An unbiased proteomics approach revealed that Chd1 interacts with several DNA repair factors including Atm, Parp1, Kap1 and Topoisomerase 2β. We show that wild-type ES cells display high levels of phosphorylated H2A.X and Kap1 at chromatin, notably at rDNA in the nucleolus, in a Chd1-dependent manner. Loss of Chd1 leads to an extensive accumulation of DSBs at Chd1-bound Pol II-transcribed genes and rDNA. Genes prone to DNA breaks in Chd1 KO ES cells tend to be longer genes with GC-rich promoters, a more labile nucleosomal structure and roles in chromatin regulation, transcription and signaling. These results reveal a vulnerability of hypertranscribing stem cells to endogenous DNA breaks, with important implications for developmental and cancer biology.

scholarly journals Soluble JAM-C Ectodomain Serves as the Niche for Adipose-Derived Stromal/Stem Cells

Biomedicines ◽  
2021 ◽  
Vol 9 (3) ◽  
pp. 278
Author(s):  
Morio Yamazaki ◽  
Kotaro Sugimoto ◽  
Yo Mabuchi ◽  
Rina Yamashita ◽  
Naoki Ichikawa-Tomikawa ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cell Adhesion ◽  
Progenitor Cells ◽  
Soluble Form ◽  
Interstitial Tissue ◽  
Stem Cell Markers ◽  
Stem And Progenitor Cells ◽  
Stromal Stem Cells

Junctional adhesion molecules (JAMs) are expressed in diverse types of stem and progenitor cells, but their physiological significance has yet to be established. Here, we report that JAMs exhibit a novel mode of interaction and biological activity in adipose-derived stromal/stem cells (ADSCs). Among the JAM family members, JAM-B and JAM-C were concentrated along the cell membranes of mouse ADSCs. JAM-C but not JAM-B was broadly distributed in the interstitial spaces of mouse adipose tissue. Interestingly, the JAM-C ectodomain was cleaved and secreted as a soluble form (sJAM-C) in vitro and in vivo, leading to deposition in the fat interstitial tissue. When ADSCs were grown in culture plates coated with sJAM-C, cell adhesion, cell proliferation and the expression of five mesenchymal stem cell markers, Cd44, Cd105, Cd140a, Cd166 and Sca-1, were significantly elevated. Moreover, immunoprecipitation assay showed that sJAM-C formed a complex with JAM-B. Using CRISPR/Cas9-based genome editing, we also demonstrated that sJAM-C was coupled with JAM-B to stimulate ADSC adhesion and maintenance. Together, these findings provide insight into the unique function of sJAM-C in ADSCs. We propose that JAMs contribute not only to cell–cell adhesion, but also to cell–matrix adhesion, by excising their ectodomain and functioning as a niche-like microenvironment for stem and progenitor cells.

scholarly journals 5-hydroxytryptamine synthesized in the aorta-gonad-mesonephros regulates hematopoietic stem and progenitor cell survival

2016 ◽  
Vol 214 (2) ◽  
pp. 529-545 ◽  
Author(s):  
Junhua Lv ◽  
Lu Wang ◽  
Ya Gao ◽  
Yu-Qiang Ding ◽  
Feng Liu
Keyword(s):  
Stem Cells ◽  
Tryptophan Hydroxylase ◽  
Ex Vivo ◽  
Great Promise ◽  
Hematopoietic Stem ◽  
Stem And Progenitor Cells ◽  
Induced Pluripotent

The in vitro or ex vivo production of transplantable hematopoietic stem cells (HSCs) holds great promise for the treatment of hematological diseases in the clinic. However, HSCs have not been produced from either embryonic or induced pluripotent stem cells. In this study, we report that 5-hydroxytryptamine (5-HT; also called serotonin) can enhance the generation of hematopoietic stem and progenitor cells (HSPCs) in vitro and is essential for the survival of HSPCs in vivo during embryogenesis. In tryptophan hydroxylase 2–deficient embryos, a decrease in 5-HT synthesized in the aorta-gonad-mesonephros leads to apoptosis of nascent HSPCs. Mechanistically, 5-HT inhibits the AKT-Foxo1 signaling cascade to protect the earliest HSPCs in intraaortic hematopoietic clusters from excessive apoptosis. Collectively, our results reveal an unexpected role of 5-HT in HSPC development and suggest that 5-HT signaling may be a potential therapeutic target for promoting HSPC survival.

Glial Cells as Progenitors and Stem Cells: New Roles in the Healthy and Diseased Brain

2014 ◽  
Vol 94 (3) ◽  
pp. 709-737 ◽  
Author(s):  
Leda Dimou ◽  
Magdalena Götz
Keyword(s):  
Stem Cells ◽  
Progenitor Cells ◽  
Glial Cells ◽  
Mammalian Brain ◽  
Radial Glial Cells ◽  
Glial Progenitors ◽  
Stem And Progenitor Cells ◽  
Radial Glial

The diverse functions of glial cells prompt the question to which extent specific subtypes may be devoted to a specific function. We discuss this by reviewing one of the most recently discovered roles of glial cells, their function as neural stem cells (NSCs) and progenitor cells. First we give an overview of glial stem and progenitor cells during development; these are the radial glial cells that act as NSCs and other glial progenitors, highlighting the distinction between the lineage of cells in vivo and their potential when exposed to a different environment, e.g., in vitro. We then proceed to the adult stage and discuss the glial cells that continue to act as NSCs across vertebrates and others that are more lineage-restricted, such as the adult NG2-glia, the most frequent progenitor type in the adult mammalian brain, that remain within the oligodendrocyte lineage. Upon certain injury conditions, a distinct subset of quiescent astrocytes reactivates proliferation and a larger potential, clearly demonstrating the concept of heterogeneity with distinct subtypes of, e.g., astrocytes or NG2-glia performing rather different roles after brain injury. These new insights not only highlight the importance of glial cells for brain repair but also their great potential in various aspects of regeneration.

Autologous transplantation of mesenchymal stem cells into the portal vein of the miniature pig; a preliminary experiment for NOTES approach

2019 ◽  
Vol 98 (9) ◽  
pp. 350-355
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Cell Therapy ◽  
Portal Vein ◽  
Liver Parenchyma ◽  
Miniature Pig ◽  
Hepatic Diseases ◽  
Study Results

Introduction: There is evidence that mesenchymal stem cells (MSCs) could trans-differentiate into the liver cells in vitro and in vivo and thus may be used as an unfailing source for stem cell therapy of liver disease. Combination of MSCs (with or without their differentiation in vitro) and minimally invasive procedures as laparoscopy or Natural Orifice Transluminal Endoscopic Surgery (NOTES) represents a chance for many patients waiting for liver transplantation in vain. Methods: Over 30 millions of autologous MSCs at passage 3 were transplanted via the portal vein in an eight months old miniature pig. The deposition of transplanted cells in liver parenchyma was evaluated histologically and the trans-differential potential of CM-DiI labeled cells was assessed by expression of pig albumin using immunofluorescence. Results: Three weeks after transplantation we detected the labeled cells (solitary, small clusters) in all 10 samples (2 samples from each lobe) but no diffuse distribution in the samples. The localization of CM-DiI+ cells was predominantly observed around the portal triads. We also detected the localization of albumin signal in CM-DiI labeled cells. Conclusion: The study results showed that the autologous MSCs (without additional hepatic differentiation in vitro) transplantation through the portal vein led to successful infiltration of intact miniature pig liver parenchyma with detectable in vivo trans-differentiation. NOTES as well as other newly developed surgical approaches in combination with cell therapy seem to be very promising for the treatment of hepatic diseases in near future.

Differentiation of mesenchymal stem cells from humans and animals into insulin-producing cells: An overview in vitro induction forms

2020 ◽  
Vol 16 ◽  
Author(s):  
Bruna O. S. Câmara ◽  
Bruno M. Bertassoli ◽  
Natália M. Ocarino ◽  
Rogéria Serakides
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Culture Medium ◽  
Adipogenic Differentiation ◽  
Medium Composition ◽  
Cell Therapies ◽  
Insulin Producing Cells ◽  
Msc Differentiation

The use of stem cells in cell therapies has shown promising results in the treatment of several diseases, including diabetes mellitus, in both humans and animals. Mesenchymal stem cells (MSCs) can be isolated from various locations, including bone marrow, adipose tissues, synovia, muscles, dental pulp, umbilical cords, and the placenta. In vitro, by manipulating the composition of the culture medium or transfection, MSCs can differentiate into several cell lineages, including insulin-producing cells (IPCs). Unlike osteogenic, chondrogenic, and adipogenic differentiation, for which the culture medium and time are similar between studies, studies involving the induction of MSC differentiation in IPCs differ greatly. This divergence is usually evident in relation to the differentiation technique used, the composition of the culture medium, the cultivation time, which can vary from a few hours to several months, and the number of steps to complete differentiation. However, although there is no “gold standard” differentiation medium composition, most prominent studies mention the use of nicotinamide, exedin-4, ß-mercaptoethanol, fibroblast growth factor b (FGFb), and glucose in the culture medium to promote the differentiation of MSCs into IPCs. Therefore, the purpose of this review is to investigate the stages of MSC differentiation into IPCs both in vivo and in vitro, as well as address differentiation techniques and molecular actions and mechanisms by which some substances, such as nicotinamide, exedin-4, ßmercaptoethanol, FGFb, and glucose, participate in the differentiation process.

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