scholarly journals The PI3k/Akt Pathway Is Associated With Angiogenesis, Oxidative Stress and Survival of Mesenchymal Stem Cells in Pathophysiologic Condition in Ischemia

2019 ◽  
pp. S131-S138 ◽  
Author(s):  
A. SAMAKOVA ◽  
A. GAZOVA ◽  
N. SABOVA ◽  
S. VALASKOVA ◽  
M. JURIKOVA ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Protein Kinase ◽  
Cell Therapy ◽  
Adult Stem Cells ◽  
Cell Types ◽  
Biologically Active ◽  
Akt Pathway ◽  
First Choice ◽  
Ischemic Diseases

Ischemic diseases are characterized by reduced blood supply to a tissue or an organ due to obstruction of blood vessels. The most serious and most common ischemic diseases include ischemic heart disease, ischemic stroke, and critical limb ischemia. Revascularization is the first choice of therapy, but the cell therapy is being introduced as a possible way of treatment for no-option patients. One of the possibilities of cell therapy is the use of mesenchymal stem cells (MSCs). MSCs are easily isolated from bone marrow and can be defined as non-hematopoietic multipotent adult stem cells population with a defined capacity for self-renewal and differentiation into cell types of all three germ layers depending on their origin. Since 1974, when Friedenstein and coworkers (Friedenstein et al. 1974) first time isolated and characterized MSCs, MSC-based therapy has been shown to be safe and effective. Nevertheless, many scientists and clinical researchers want to improve the success of MSCs in regenerative therapy. The secret of successful cell therapy may lie, along with the homing, in secretion of biologically active molecules including cytokines, growth factors, and chemokines known as MSCs secretome. One of the intracellular signalling mechanism includes the activity of phosphatidylinositol-3-kinase (phosphoinositide 3-kinase) (PI3K) - protein kinase B (serine-threonine protein kinase Akt) (Akt) pathway. This PI3K/Akt pathway plays key roles in many cell types in regulating cell proliferation, differentiation, apoptosis, and migration. Pre-conditioning of MSCs could improve efficacy of signalling mechanism.

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

2011 ◽  
Vol 2011 ◽  
pp. 1-18 ◽  
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.

scholarly journals Mesenchymal Stem Cells Isolated from Adipose and Other Tissues: Basic Biological Properties and Clinical Applications

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Hakan Orbay ◽  
Morikuni Tobita ◽  
Hiroshi Mizuno
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Adult Stem Cells ◽  
Cell Types ◽  
Biological Properties ◽  
Clinical Applications ◽  
Therapeutic Tool ◽  
Adult Tissues ◽  
Clinical Benefits ◽  
Multiple Cell

Mesenchymal stem cells (MSCs) are adult stem cells that were initially isolated from bone marrow. However, subsequent research has shown that other adult tissues also contain MSCs. MSCs originate from mesenchyme, which is embryonic tissue derived from the mesoderm. These cells actively proliferate, giving rise to new cells in some tissues, but remain quiescent in others. MSCs are capable of differentiating into multiple cell types including adipocytes, chondrocytes, osteocytes, and cardiomyocytes. Isolation and induction of these cells could provide a new therapeutic tool for replacing damaged or lost adult tissues. However, the biological properties and use of stem cells in a clinical setting must be well established before significant clinical benefits are obtained. This paper summarizes data on the biological properties of MSCs and discusses current and potential clinical applications.

scholarly journals Cell therapies for traumatic brain injury

2008 ◽  
Vol 24 (3-4) ◽  
pp. E18 ◽  
Author(s):  
Matthew T. Harting ◽  
James E. Baumgartner ◽  
Laura L. Worth ◽  
Linda Ewing-Cobbs ◽  
Adrian P. Gee ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Stem Cells ◽  
Clinical Trials ◽  
Brain Injury ◽  
Cell Therapy ◽  
Adult Stem Cells ◽  
Cell Types ◽  
Current Status ◽  
Cell Therapies ◽  
Current Therapies

Preliminary discoveries of the efficacy of cell therapy are currently being translated to clinical trials. Whereas a significant amount of work has been focused on cell therapy applications for a wide array of diseases, including cardiac disease, bone disease, hepatic disease, and cancer, there continues to be extraordinary anticipation that stem cells will advance the current therapeutic regimen for acute neurological disease. Traumatic brain injury is a devastating event for which current therapies are limited. In this report the authors discuss the current status of using adult stem cells to treat traumatic brain injury, including the basic cell types and potential mechanisms of action, preclinical data, and the initiation of clinical trials.

scholarly journals CD90- (Thy-1-) High Selection Enhances Reprogramming Capacity of Murine Adipose-Derived Mesenchymal Stem Cells

2013 ◽  
Vol 35 ◽  
pp. 573-579 ◽  
Author(s):  
Koichi Kawamoto ◽  
Masamitsu Konno ◽  
Hiroaki Nagano ◽  
Shimpei Nishikawa ◽  
Yoshito Tomimaru ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Cell Therapy ◽  
Tolerance Induction ◽  
Cell Types ◽  
Effective Strategy ◽  
Cell Sorter ◽  
High Selection ◽  
Selection Of

Background. Mesenchymal stem cells (MSCs), including adipose tissue-derived mesenchymal stem cells (ADSC), are multipotent and can differentiate into various cell types possessing unique immunomodulatory features. Several clinical trials have demonstrated the safety and possible efficacy of MSCs in organ transplantation. Thus, stem cell therapy is promising for tolerance induction. In this study, we assessed the reprogramming capacity of murine ADSCs and found that CD90 (Thy-1), originally discovered as a thymocyte antigen, could be a useful marker for cell therapy.Method. Murine ADSCs were isolated from B6 mice, sorted using a FACSAria cell sorter by selection ofCD90HiorCD90Lo, and then transduced with four standard factors (4F; Oct4, Sox2, Klf4, and c-Myc).Results. Unsorted,CD90Hi-sorted, andCD90Lo-sorted murine ADSCs were reprogrammed using standard 4F transduction.CD90HiADSCs showed increased numbers of alkaline phosphatase-positive colonies compared withCD90LoADSCs. The relative reprogramming efficiencies of unsorted,CD90Hi-sorted, andCD90Lo-sorted ADSCs were 100%, 116.5%, and 74.7%, respectively.CD90Hicells were more responsive to reprogramming.Conclusion.CD90HiADSCs had greater reprogramming capacity thanCD90LoADSCs, suggesting that ADSCs have heterogeneous subpopulations. Thus,CD90Hiselection presents an effective strategy to isolate a highly suppressive subpopulation for stem cell-based tolerance induction therapy.

Progress of Mesenchymal Stem Cell-Derived Exosomes in Tissue Repair

2020 ◽  
Vol 26 (17) ◽  
pp. 2022-2037 ◽  
Author(s):  
Guifang Zhao ◽  
Yiwen Ge ◽  
Chenyingnan Zhang ◽  
Leyi Zhang ◽  
Junjie Xu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Cell Therapy ◽  
Tissue Repair ◽  
Inflammatory Responses ◽  
Biologically Active ◽  
Research Progress ◽  
Tissue Specific

Mesenchymal stem cells (MSCs) are a kind of adult stem cells with self-replication and multidirectional differentiation, which can differentiate into tissue-specific cells under physiological conditions, maintaining tissue self-renewal and physiological functions. They play a role in the pathological condition by lateral differentiation into tissue-specific cells, replacing damaged tissue cells by playing the role of a regenerative medicine , or repairing damaged tissues through angiogenesis, thereby, regulating immune responses, inflammatory responses, and inhibiting apoptosis. It has become an important seed cell for tissue repair and organ reconstruction, and cell therapy based on MSCs has been widely used clinically. The study found that the probability of stem cells migrating to the damaged area after transplantation or differentiating into damaged cells is very low, so the researchers believe the leading role of stem cell transplantation for tissue repair is paracrine secretion, secreting growth factors, cytokines or other components. Exosomes are biologically active small vesicles secreted by MSCs. Recent studies have shown that they can transfer functional proteins, RNA, microRNAs, and lncRNAs between cells, and greatly reduce the immune response. Under the premise of promoting proliferation and inhibition of apoptosis, they play a repair role in tissue damage, which is caused by a variety of diseases. In this paper, the biological characteristics of exosomes (MSCs-exosomes) derived from mesenchymal stem cells, intercellular transport mechanisms, and their research progress in the field of stem cell therapy are reviewed.

SDF-1 secreted by mesenchymal stem cells promotes the migration of endothelial progenitor cells via PI3K/Akt pathway

2020 ◽  
Author(s):  
Xiaoyi Wang ◽  
Huijiao Jiang ◽  
Lijiao Guo ◽  
Sibo Wang ◽  
Wenzhe Cheng ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Cell Therapy ◽  
Progenitor Cells ◽  
Structure Formation ◽  
Endothelial Progenitor Cells ◽  
Hind Limb ◽  
Capillary Density ◽  
Akt Pathway ◽  
Paracrine Action

Abstract Background: Cell-based therapeutics bring great hope in areas of unmet medical needs. Mesenchymal stem cells (MSCs) has been suggested to facilitate neovascularization mainly by paracrine action, and endothelial progenitor cells (EPCs) can differentiate into mature endothelial cells. Studies have demonstrated that a combination cell therapy that includes MSCs and EPCs has a favorable effect on ischemic limbs. However, the mechanism of combination cell therapy remains unclear. Herein, we investigate whether stromal cell-derived factor (SDF)-1 secreted by MSCs contributes to. Furthermore, we examined whether SDF-1 affects EPC migration via Phosphoinositide 3-Kinases (PI3K)/protein kinase B (termed as Akt) signaling pathway.Methods: First, intramuscular MSC injections were supplemented with intravenous EPC injections in the mouse model of hind limb ischemia. The incorporation of Qdot® 525 labeled-EPC into the vasculature and capillary density was evaluated by CD31 immunohistochemistry and immunofluorescence, respectively. Then, the concentration of SDF-1 secreted by MSCs was detected via quantitative immunoassay. Flow cytometry was performed to quantify CXC chemokine receptor (CXCR) 4-positive EPCs. The effect of MSCs on EPC migration was measured by a transwell system and a tube-like structure formation on Matrigel. The SDF-1 antagonist AMD3100 and the PI3K inhibitor wortmannin were separately used to determine the participation of CXCR4 and PI3K into EPC migration. Finally, western blot assay was performed to detect the effect of SDF-1 secreted by MSCs on Akt phosphorylation in EPCs.Results: The combination delivery of MSCs and EPCs via a “dual-administration” approach enhanced the incorporation of EPCs into the vasculature and increased the capillary density in mouse ischemic hind limb. The SDF-1 concentration secreted by MSCs was 2.61 ng/ml after 48 h. CXCR4-positive EPCs increased after incubation with MSC-conditioned medium (CM). MSCs contributed to EPC migration and tube-like structure formation, both of which were suppressed by AMD3100 and wortmannin. Phospho-Akt induced by MSC-CM was attenuated when EPCs were pretreated with AMD3100 and wortmannin.Conclusions: The paracrine action of MSCs contributes to EPC migration. Furthermore, SDF-1 secreted by MSCs induces EPC migration. The mechanism of this migration is related to the activation of the Akt pathway

Therapeutic potential of transdifferentiated cells

2005 ◽  
Vol 108 (4) ◽  
pp. 309-321 ◽  
Author(s):  
Zoë D. BURKE ◽  
David TOSH
Keyword(s):  
Stem Cells ◽  
Cell Therapy ◽  
Adult Stem Cells ◽  
Therapeutic Potential ◽  
Cell Types ◽  
Therapeutic Modality ◽  
Differentiated Cells ◽  
Degenerative Disorders ◽  
Clinical Conditions

Cell therapy means treating diseases with the body's own cells. The ability to produce differentiated cell types at will offers a compelling new approach to cell therapy and therefore for the treatment and cure of a plethora of clinical conditions, including diabetes, Parkinson's disease and cardiovascular disease. Until recently, it was thought that differentiated cells could only be produced from embryonic or adult stem cells. Although the results from stem cell studies have been encouraging, perhaps the most startling findings have been the recent observations that differentiated cell types can transdifferentiate (or convert) into a completely different phenotype. Harnessing transdifferentiated cells as a therapeutic modality will complement the use of embryonic and adult stem cells in the treatment of degenerative disorders. In this review, we will examine some examples of transdifferentiation, describe the theoretical and practical issues involved in transdifferentiation research and comment on the long-term therapeutic possibilities.

scholarly journals Reciprocal interaction between mesenchymal stem cells and transit amplifying cells regulates tissue homeostasis

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Junjun Jing ◽  
Jifan Feng ◽  
Jingyuan Li ◽  
Hu Zhao ◽  
Thach-Vu Ho ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Wnt Signaling ◽  
Adult Stem Cells ◽  
Cell Types ◽  
Tissue Homeostasis ◽  
Canonical Wnt Signaling ◽  
Multiple Organs ◽  
Canonical Wnt

Interaction between adult stem cells and their progeny is critical for tissue homeostasis and regeneration. In multiple organs, mesenchymal stem cells (MSCs) give rise to transit amplifying cells (TACs), which then differentiate into different cell types. However, whether and how MSCs interact with TACs remains unknown. Using the adult mouse incisor as a model, we present in vivo evidence that TACs and MSCs have distinct genetic programs and engage in reciprocal signaling cross talk to maintain tissue homeostasis. Specifically, an IGF-WNT signaling cascade is involved in the feedforward from MSCs to TACs. TACs are regulated by tissue-autonomous canonical WNT signaling and can feedback to MSCs and regulate MSC maintenance via Wnt5a/Ror2-mediated non-canonical WNT signaling. Collectively, these findings highlight the importance of coordinated bidirectional signaling interaction between MSCs and TACs in instructing mesenchymal tissue homeostasis, and the mechanisms identified here have important implications for MSC–TAC interaction in other organs.

scholarly journals Dental Tissue-Derived Stem Cells as a Candidate for Neural Regeneration

2017 ◽  
Vol 3 ◽  
pp. 69 ◽  
Author(s):  
Samira Malekzadeh ◽  
Mohammad Amin Edalatmanesh ◽  
Davood Mehrabani ◽  
Mehrdad Shariati ◽  
Sima Malekzadeh
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Cell Therapy ◽  
Cell Types ◽  
Review Article ◽  
Neural Regeneration ◽  
Dental Stem Cells ◽  
Dental Tissue ◽  
Dental Tissues

In recent years, stem cell therapy tried to improve the life of patients that suffer from neurodegenerative disease, like Alzheimer's disease. Although teeth are non-essential for life, but the dental tissues are an important source of mesenchymal stem cells that are suitable for neural regeneration. The studies showed that dental stem cells (DSCs) have the potential to differentiate into several cell types that among the most important is neural progenitor. In this review article, discusses the types of dental stem cells and then focused on application of dental stem cells on neural regeneration.

scholarly journals The Holy Grail of Orthopedic Surgery: Mesenchymal Stem Cells—Their Current Uses and Potential Applications

2017 ◽  
Vol 2017 ◽  
pp. 1-14 ◽  
Author(s):  
Roberto Berebichez-Fridman ◽  
Ricardo Gómez-García ◽  
Julio Granados-Montiel ◽  
Enrique Berebichez-Fastlicht ◽  
Anell Olivos-Meza ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Orthopedic Surgery ◽  
Adult Stem Cells ◽  
Spinal Cord Injuries ◽  
Cell Types ◽  
Cartilage Defects ◽  
Medical Specialties ◽  
Potential Applications

Only select tissues and organs are able to spontaneously regenerate after disease or trauma, and this regenerative capacity diminishes over time. Human stem cell research explores therapeutic regenerative approaches to treat various conditions. Mesenchymal stem cells (MSCs) are derived from adult stem cells; they are multipotent and exert anti-inflammatory and immunomodulatory effects. They can differentiate into multiple cell types of the mesenchyme, for example, endothelial cells, osteoblasts, chondrocytes, fibroblasts, tenocytes, vascular smooth muscle cells, and sarcomere muscular cells. MSCs are easily obtained and can be cultivated and expanded in vitro; thus, they represent a promising and encouraging treatment approach in orthopedic surgery. Here, we review the application of MSCs to various orthopedic conditions, namely, orthopedic trauma; muscle injury; articular cartilage defects and osteoarthritis; meniscal injuries; bone disease; nerve, tendon, and ligament injuries; spinal cord injuries; intervertebral disc problems; pediatrics; and rotator cuff repair. The use of MSCs in orthopedics may transition the practice in the field from predominately surgical replacement and reconstruction to bioregeneration and prevention. However, additional research is necessary to explore the safety and effectiveness of MSC treatment in orthopedics, as well as applications in other medical specialties.

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