scholarly journals The Role of MSCs and Cell Fusion in Tissue Regeneration

2021 ◽  
Vol 22 (20) ◽  
pp. 10980
Author(s):  
Jessica Dörnen ◽  
Thomas Dittmar
Keyword(s):  
Immune Response ◽  
Regenerative Medicine ◽  
Cell Fusion ◽  
Tissue Regeneration ◽  
Stromal Cells ◽  
Clinical Studies ◽  
Therapeutic Agents ◽  
Immunomodulatory Capacity ◽  
Additional Process

Regenerative medicine is concerned with the investigation of therapeutic agents that can be used to promote the process of regeneration after injury or in different diseases. Mesenchymal stem/stromal cells (MSCs) and their secretome – including extracellular vesicles (EVs) are of great interest, due to their role in tissue regeneration, immunomodulatory capacity and low immunogenicity. So far, clinical studies are not very conclusive as they show conflicting efficacies regarding the use of MSCs. An additional process possibly involved in regeneration might be cell fusion. This process occurs in both a physiological and a pathophysiological context and can be affected by immune response due to inflammation. In this review the role of MSCs and cell fusion in tissue regeneration is discussed.

scholarly journals Is Immune Modulation the Mechanism Underlying the Beneficial Effects of Amniotic Cells and Their Derivatives in Regenerative Medicine?

2017 ◽  
Vol 26 (4) ◽  
pp. 531-539 ◽  
Author(s):  
Antonietta R. Silini ◽  
Marta Magatti ◽  
Anna Cargnoni ◽  
Ornella Parolini
Keyword(s):  
Immune Response ◽  
Regenerative Medicine ◽  
Amniotic Membrane ◽  
Stromal Cells ◽  
Immune Modulation ◽  
Cell Replacement ◽  
Beneficial Effects ◽  
Repair Mechanisms ◽  
Altered Immune Response ◽  
Amniotic Cells

Regenerative medicine aims to repair and regenerate damaged cells, tissues, and organs in order to restore function. Regeneration can be obtained either by cell replacement or by stimulating the body's own repair mechanisms. Importantly, a favorable environment is required before any regenerative signal can stimulate resident stem/stromal cells, and regeneration is possible only after the resolution of injury-induced inflammation. An exacerbated immune response is often present in cases of degenerative, inflammatory-based diseases. Here we discuss how amniotic membrane cells, and their derivatives, can contribute to the resolution of many diseases with altered immune response by acting on different inflammatory mediators.

scholarly journals The Role of Animal Models in Evaluating Reasonable Safety and Efficacy for Human Trials of Cell-Based Interventions for Neurologic Conditions

2008 ◽  
Vol 29 (1) ◽  
pp. 1-9 ◽  
Author(s):  
Alan Regenberg ◽  
Debra JH Mathews ◽  
David M Blass ◽  
Hilary Bok ◽  
Joseph T Coyle ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Animal Models ◽  
Regenerative Medicine ◽  
Therapeutic Agents ◽  
Preclinical Studies ◽  
Safety And Efficacy ◽  
Proper Role ◽  
New Treatments ◽  
Gathering Data

Progress in regenerative medicine seems likely to produce new treatments for neurologic conditions that use human cells as therapeutic agents; at least one trial for such an intervention is already under way. The development of cell-based interventions for neurologic conditions (CBI-NCs) will likely include preclinical studies using animals as models for humans with conditions of interest. This paper explores predictive validity challenges and the proper role for animal models in developing CBI-NCs. In spite of limitations, animal models are and will remain an essential tool for gathering data in advance of first-in-human clinical trials. The goal of this paper is to provide a realistic lens for viewing the role of animal models in the context of CBI-NCs and to provide recommendations for moving forward through this challenging terrain.

Virtual role of ex-vivo expanded human mesenchymal stromal cells after transplantation into bone tissue regeneration model

Bone ◽  
2012 ◽  
Vol 50 ◽  
pp. S84
Author(s):  
Ri youn Kim⁎ ◽  
Tae Hyung Cho ◽  
Yun Mi Song ◽  
Ji Hye Oh ◽  
Beom Seok Lee ◽  
...  
Keyword(s):  
Bone Tissue ◽  
Mesenchymal Stromal Cells ◽  
Tissue Regeneration ◽  
Stromal Cells ◽  
Ex Vivo ◽  
Bone Tissue Regeneration ◽  
Human Mesenchymal Stromal Cells

scholarly journals Safety of Mesenchymal Stem Cells for Clinical Application

2012 ◽  
Vol 2012 ◽  
pp. 1-4 ◽  
Author(s):  
Youwei Wang ◽  
Zhi-bo Han ◽  
Yong-ping Song ◽  
Zhong Chao Han
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Regenerative Medicine ◽  
Therapeutic Agents ◽  
Great Promise ◽  
Safety Issues ◽  
Human Use

Mesenchymal stem cells (MSCs) hold great promise as therapeutic agents in regenerative medicine and autoimmune diseases, based on their differentiation abilities and immunosuppressive properties. However, the therapeutic applications raise a series of questions about the safety of culture-expanded MSCs for human use. This paper summarized recent findings about safety issues of MSCs, in particular their genetic stability in long-termin vitroexpansion, their cryopreservation, banking, and the role of serum in the preparation of MSCs.

scholarly journals MicroRNAs as Important Regulators Mediate the Multiple Differentiation of Mesenchymal Stromal Cells

2021 ◽  
Vol 9 ◽  
Author(s):  
Chao Yang ◽  
Maowen Luo ◽  
Yu Chen ◽  
Min You ◽  
Qiang Chen
Keyword(s):  
Regenerative Medicine ◽  
Stromal Cells ◽  
Critical Role ◽  
The Body ◽  
Disease Treatment ◽  
Multipotent Stem Cells ◽  
Physiological Processes ◽  
Multiple Differentiation ◽  
Differentiation Efficiency

MicroRNAs (miRNAs) are endogenous short non-encoding RNAs which play a critical role on the output of the proteins, and influence multiple biological characteristics of the cells and physiological processes in the body. Mesenchymal stem/stromal cells (MSCs) are adult multipotent stem cells and characterized by self-renewal and multidifferentiation and have been widely used for disease treatment and regenerative medicine. Meanwhile, MSCs play a critical role in maintaining homeostasis in the body, and dysfunction of MSC differentiation leads to many diseases. The differentiation of MSCs is a complex physiological process and is the result of programmed expression of a series of genes. It has been extensively proven that the differentiation process or programmed gene expression is also regulated accurately by miRNAs. The differentiation of MSCs regulated by miRNAs is also a complex, interdependent, and dynamic process, and a full understanding of the role of miRNAs will provide clues on the appropriate upregulation or downregulation of corresponding miRNAs to mediate the differentiation efficiency. This review summarizes the roles and associated signaling pathways of miRNAs in adipogenesis, chondrogenesis, and osteogenesis of MSCs, which may provide new hints on MSCs or miRNAs as therapeutic strategies for regenerative medicine and biotherapy for related diseases.

scholarly journals Sphingolipids as Mediators in the Crosstalk between Microbiota and Intestinal Cells: Implications for Inflammatory Bowel Disease

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Phillips-Farfán Bryan ◽  
Carvajal Karla ◽  
Medina-Torres Edgar Alejandro ◽  
Espinosa-Padilla Sara Elva ◽  
Fabrias Gemma ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Immune Response ◽  
Immune System ◽  
Gut Microbiota ◽  
Bowel Disease ◽  
Therapeutic Agents ◽  
Intestinal Cells ◽  
Intestinal Immunity ◽  
Inflammatory Bowel

Inflammatory bowel disease (IBD) describes different illnesses characterized by chronic inflammation of the gastrointestinal tract. Although the pathogenic mechanisms leading to IBD are poorly understood, immune system disturbances likely underlie its development. Sphingolipids (SLs) have been identified as important players and promising therapeutic targets to control inflammation in IBD. Interestingly, it seems that microorganisms of the normal gut microbiota and probiotics are involved in sphingolipid function. However, there is a great need to investigate the role of SLs as intermediates in the crosstalk between intestinal immunity and microorganisms. This review focuses on recent investigations that describe some mechanisms involved in the regulation of cytokine profiles by SLs. We also describe the importance of gut microbiota in providing signaling molecules that favor the communication between resident bacteria and intestinal cells. This, in turn, modulates the immune response in the bowel and likely in other peripheral organs. The potential of SLs and gut microbiota as targets or therapeutic agents for IBD is also discussed.

scholarly journals Wound Healing Versus Regeneration: Role of the Tissue Environment in Regenerative Medicine

MRS Bulletin ◽  
2010 ◽  
Vol 35 (8) ◽  
pp. 597-606 ◽  
Author(s):  
Anthony Atala ◽  
Darrell J. Irvine ◽  
Marsha Moses ◽  
Sunil Shaunak
Keyword(s):  
Extracellular Matrix ◽  
Wound Healing ◽  
Regenerative Medicine ◽  
Tissue Regeneration ◽  
Normal Tissue ◽  
Disease Process ◽  
Scar Formation ◽  
The Body ◽  
Mechanistic Basis

AbstractOne of the major challenges in the field of regenerative medicine is how to optimize tissue regeneration in the body by therapeutically manipulating its natural ability to form scar at the time of injury or disease. It is often the balance between tissue regeneration, a process that is activated at the onset of disease, and scar formation, which develops as a result of the disease process that determines the ability of the tissue or organ to be functional. Using biomaterials as scaffolds often can provide a “bridge” for normal tissue edges to regenerate over small distances, usually up to 1 cm. Larger tissue defect gaps typically require both scaffolds and cells for normal tissue regeneration to occur without scar formation. Various strategies can help to modulate the scar response and can potentially enhance tissue regeneration. Understanding the mechanistic basis of such multivariate interactions as the scar microenvironment, the immune system, extracellular matrix, and inflammatory cytokines may enable the design of tissue engineering and wound healing strategies that directly modulate the healing response in a manner favorable to regeneration.

scholarly journals Extra-hematopoietic immunomodulatory role of the SCID-susceptibility gene DOCK-2 identified by stepwise maturation of human iPSCs into clonogenic mesodermal stromal progenitors

2020 ◽  
Author(s):  
Cornelia Scharler ◽  
Rodolphe Poupardin ◽  
Patricia Peking ◽  
Martin Wolf ◽  
Gabriele Brachtl ◽  
...  
Keyword(s):  
Stromal Cells ◽  
Immune Cell ◽  
Severe Combined Immunodeficiency ◽  
Susceptibility Gene ◽  
Stromal Fibroblast ◽  
Immune Gene ◽  
Hematopoietic Stem ◽  
Human Ipscs ◽  
Immunomodulatory Capacity

ABSTRACTStromal cells contribute to organ integrity as fibroblasts and to vascular stability as pericytes, in addition to their enigmatic niche function in many tissues. Their inherent immunomodulatory capacity attracted particular attention, initiating numerous clinical trials, particularly testing trophic regeneration and immunomodulation. Key stromal immune functions are still enigmatic.Here we show that dedicator of cytokinesis (DOCK-2) previously described for causing immune cell dysfunction plays a role in extra-hematopoietic immunity by regulating stromal/fibroblast immunomodulatory function. We used three independent strategies including iPSC-derived mesodermal stromal cell (MSC) lineage maturation, severe combined immunodeficiency (SCID) patient-derived cells and CRISPR/Cas9 knockout to support our findings.Human induced pluripotent stem cells (iPSCs) were generated from healthy bone marrow and umbilical cord blood-derived fibroblasts by Sendai virus-mediated transient expression of Yamanaka factors. After mesoderm induction, stromal differentiation was induced by platelet-derived growth factors under animal serum-free conditions. Under feeder-free defined conditions, iPSCs differentiated into expandable and cryo-preservable CD73+/CD105+/Tra-1-81− early iPS-MSCs lacking immunosuppressive potential. Successive maturation was required for reaching the canonical MSC phenotype and immunomodulatory competence over time, while maintaining clonogenicity, comparable to parental MSCs. Sequential RNAseq revealed acquisition of a spectrum of immune-related genes significantly expressed in mature iPS-MSCs and resembling parental MSC’s immune gene expression. The DOCK-2 gene attracted our attention because mutations can cause SCID. Interestingly, SCID patient-derived fibroblast lines harboring bi-allelic DOCK-2 mutations showed significantly reduced immunomodulatory capacity compared to non-mutated control fibroblasts. CRISPR/Cas9-mediated DOCK-2 knockout in healthy iPSCs resulted in iPS-MSCs that also displayed reduced immunomodulatory capacity, thus confirming a role of DOCK-2 in stromal immune function. At a mechanistic level, DOCK-2 deficiency resulted in disturbed subcellular localization of CDC42.This provides first evidence for an extra-hematopoietic immunomodulatory role of DOCK-2 in stromal cells, previously considered restricted to hampering immune cell migration/function resulting in SCID. We may speculate that some of the signs and symptoms of persisting immune disease after successful hematopoietic stem cell transplantation in SCID patients could at least in part be due to mutations, like DOCK-2−/−, permissive outside the hematopoietic immune system, as evidenced also by the increased virus infection susceptibility of DOCK-2 deficient fibroblasts.

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