Bone Marrow Mesenchymal Stromal Cells: Identification, Classification, and Differentiation

Bone marrow mesenchymal stromal cells (BMSCs), identified as pericytes comprising the hematopoietic niche, are a group of heterogeneous cells composed of multipotent stem cells, including osteochondral and adipocyte progenitors. Nevertheless, the identification and classification are still controversial, which limits their application. In recent years, by lineage tracing and single-cell sequencing, several new subgroups of BMSCs and their roles in normal physiological and pathological conditions have been clarified. Key regulators and mechanisms controlling the fate of BMSCs are being revealed. Cross-talk among subgroups of bone marrow mesenchymal cells has been demonstrated. In this review, we focus on recent advances in the identification and classification of BMSCs, which provides important implications for clinical applications.

Modulation of Mesenchymal Stem Cells for Enhanced Therapeutic Utility in Ischemic Vascular Diseases

Mesenchymal stem cells are multipotent stem cells isolated from various tissue sources, including but not limited to bone marrow, adipose, umbilical cord, and Wharton Jelly. Although cell-mediated mechanisms have been reported, the therapeutic effect of MSCs is now recognized to be primarily mediated via paracrine effects through the secretion of bioactive molecules, known as the “secretome”. The regenerative benefit of the secretome has been attributed to trophic factors and cytokines that play neuroprotective, anti-angiogenic/pro-angiogenic, anti-inflammatory, and immune-modulatory roles. The advancement of autologous MSCs therapy can be hindered when introduced back into a hostile/disease environment. Barriers include impaired endogenous MSCs function, limited post-transplantation cell viability, and altered immune-modulatory efficiency. Although secretome-based therapeutics have gained popularity, many translational hurdles, including the heterogeneity of MSCs, limited proliferation potential, and the complex nature of the secretome, have impeded the progress. This review will discuss the experimental and clinical impact of restoring the functional capabilities of MSCs prior to transplantation and the progress in secretome therapies involving extracellular vesicles. Modulation and utilization of MSCs–secretome are most likely to serve as an effective strategy for promoting their ultimate success as therapeutic modulators.

Intestinal Enteroid Monolayers Model the Human Intestinal Environment for Escherichia coli Infection

Enterohemorrhagic Escherichia coli O157:H7 is an enteric pathogen responsible for bloody diarrhea, hemolytic uremic syndrome, and in severe cases even death. The study of O157:H7 is difficult due to the high specificity of the bacteria for the human intestine, along with our lack of sufficiently complex human cell culture models. The recent development of human intestinal enteroids derived from intestinal crypt multipotent stem cells has allowed us to construct 2-dimensional differentiated epithelial monolayers grown in transwells that mimic the human intestine. Unlike previous studies, saline was added to the apical surface, while maintaining culture media in the basolateral well. The monolayers continued to grow and differentiate with apical saline. Apical infection with O157:H7 or commensal E. coli resulted in robust bacterial growth from 105 to over 108 over 24 hours. Despite this robust bacterial growth, commensal E. coli neither adhered to nor damaged the epithelial barrier over 30 hours. However, O157:H7 was almost fully adhered (>90%) by 18 hours with epithelial damage observed by 30 hours. O157:H7 contains the locus of enterocyte effacement (LEE) pathogenicity island responsible for attachment and damage to the intestinal epithelium. Previous studies report the ability of nutrients such as biotin, D-serine, and L-fucose to downregulate LEE gene expression. O157:H7 treated with biotin or L-fucose, but not D-serine displayed both decreased attachment and reduced epithelial damage over 36 hours. These data illustrate enteroid monolayers can serve as a suitable model for the study of O157:H7 pathogenesis, and identification of potential therapeutics.

Hematopoietic Stem Cell Transplantation (HSCT): Its History, Evolution and Future Perspectives in Evolving World

The Hematopoietic Stem Cell Transplantation (HSCT) is known to be a very complex practice which involves the transplantation of multipotent stem cells from a donor to the recipient. For the very recent time period this field has changed into its better form i.e. it has immensely proved itself for the medical care of certain hematological as well as immune-deficiency syndromes. Right now, HSCT is a broadly acknowledged treatment for some dangerous illnesses. It in this manner addresses a genuine helpful expect numerous patients. Due to this widening latitude of transplantation, it has certainly drawn the attention of medical crowd as it now being synchronized in many parts of the world. The present work provides a review of the development strategies of HSCT.

Effects of Alginate Encapsulation on the Vertebral Bone Adherent Mesenchymal Stromal Cell Paracrine Secretome

Background/Objectives: Mesenchymal stromal cells (MSCs) are spindle-shaped multipotent stem cells that can be found in any vascularized organ especially bone marrow, adipose tissue, and cord blood. MSCs have pro-angiogenic and myogenic properties which have been proposed as a potential treatment for preventing limb amputations in patients with critical limb threatening ischemia (CLTI) due to peripheral artery disease (PAD) and diabetes mellitus. Allogeneic MSCs from a young healthy donor may decrease the risk of amputation by promoting angiogenesis and muscle regeneration. However, their potency may be limited by host immune reactions to allogeneic cells. Encapsulating MSCs in a hydrogel may help to protect transplanted MSCs from the immune system of the host. Additionally, encapsulation may enhance the secretion of anti-inflammatory and pro-angiogenic factors from MSCs. Some of the molecules involved in fighting inflammation and promoting angiogenesis include interleukin (IL)-10, IL-33, hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF), and angiopoietin-1. Methods. For the encapsulation group, MSCs were centrifuged in a 2% alginate solution through a needle and into a calcium chloride bath. Both unencapsulated and encapsulated MSCs were incubated for 48 hours in various conditions including normoxia, normoxia with high glucose (diabetic mimic), hypoxia, and hypoxia with high glucose. The media was then harvested and analyzed using enzyme-linked immunosorbent assays (ELISAs) (R&D Systems, MN) for IL-10, HGF, VEGF, and angiopoietin-1. Results. No detectable levels of IL-10, HGF, or angiopoietin-1 were found in either cell media group. VEGF levels were significantly elevated in hypoxic high glucose conditions compared to normoxic and normoxic high glucose conditions within the unencapsulated group. Discussion. These results demonstrate that hypoxic high glucose conditions duplicating ischemic diabetic muscle amplify MSC VEGF secretion. The next step is to run a VEGF ELISA on the encapsulated cell media group and compare those results to the unencapsulated cell media group. WC: 300

Mesenchymal Stem Cells Versus Covid-19. Can They Win the Battle?

Mesenchymal stem cells (MSCs) are multipotent stem cells with numerous features potentially useful in various pathologies. It has been shown that MSCs have regenerative potential due to modulation of immune system response, inflammation diminishing, trans differentiation into various types of cells, proangiogenetic and anti fibrotic influence. Besides all of these traits, MSCs posses anti viral capacity and have been further employed in clinical trails since last year. Here, we revised immunomodulatory, biological and antiviral traits of MSCs, but also pathogenesis of Covid-19 and it’s impact on immune system. Conspicuously, there is a growing number of studies examining effect of MSCs in patients suffering from Covid-19 pneumonia and ARDS. Since MSCs are in theory capable of healing lung injury and inflammation, here we discuss hypothesis, pros and cons of MSCs treatment in Covid-19 patients. Finally, we debate if MSCs based therapy can be promising tool for Covid-19 lung pathologies.

Role of Signaling Pathways during Cardiomyocyte Differentiation of Mesenchymal Stem Cells

Multipotent stem cells, including mesenchymal stem cells (MSCs), represent a promising source to be used by regenerative medicine. They are capable of performing myogenic, chondrogenic, osteogenic and adipogenic differentiation. Also, MSCs are characterized by the expression of multiple surface antigens, but none of them appears to be particularly expressed on MSCs. Moreover, the prospect of monitoring and controlling MSC differentiation is a scientifically crucial regulatory and clinical requirement. Different transcription factors and signaling pathways are involved in cardiomyocyte differentiation. Due to the paucity of studies exclusively focused on cardiomyocyte differentiation of MSCs, present study aims at describing the roles of various signaling pathways (FGF, TGF, Wnt, Notch, etc.) in cardiomyocytes differentiation of MSCs. Understanding the signaling pathways that control the commitment and differentiation of cardiomyocyte cells not only will expand our basic understanding of molecular mechanisms of heart development, but also will enable us to develop therapeutic means of intervention in cardiovascular diseases.

Differentiation of adipose-derived stem cells to chondrocytes using electrospraying

An important challenge in the fabrication of tissue engineered constructs for regenerative medical applications is the development of processes capable of delivering cells and biomaterials to specific locations in a consistent manner. Electrospraying live cells has been introduced in recent years as a cell seeding method, but its effect on phenotype nor genotype has not been explored. A promising candidate for the cellular component of these constructs are human adipose-derived stem cells (hASCs), which are multipotent stem cells that can be differentiated into fat, bone, and cartilage cells. They can be easily and safely obtained from adipose tissue, regardless of the age and sex of the donor. Moreover, these cells can be maintained and expanded in culture for long periods of time without losing their differentiation capacity. In this study, hASCs directly incorporated into a polymer solution were electrosprayed, inducing differentiation into chondrocytes, without the addition of any exogenous factors. Multiple studies have demonstrated the effects of exposing hASCs to biomolecules—such as soluble growth factors, chemokines, and morphogens—to induce chondrogenesis. Transforming growth factors (e.g., TGF-β) and bone morphogenetic proteins are particularly known to play essential roles in the induction of chondrogenesis. Although growth factors have great therapeutic potential for cell-based cartilage regeneration, these growth factor-based therapies have presented several clinical complications, including high dose requirements, low half-life, protein instability, higher costs, and adverse effects in vivo. The present data suggests that electrospraying has great potential as hASCs-based therapy for cartilage regeneration.

Mesenchymal Stem Cell: A Friend or Foe in Anti-Tumor Immunity

Mesenchymal stem cells (MSCs) are self-renewable, multipotent stem cells that regulate the phenotype and function of all immune cells that participate in anti-tumor immunity. MSCs modulate the antigen-presenting properties of dendritic cells, affect chemokine and cytokine production in macrophages and CD4+ T helper cells, alter the cytotoxicity of CD8+ T lymphocytes and natural killer cells and regulate the generation and expansion of myeloid-derived suppressor cells and T regulatory cells. As plastic cells, MSCs adopt their phenotype and function according to the cytokine profile of neighboring tumor-infiltrated immune cells. Depending on the tumor microenvironment to which they are exposed, MSCs may obtain pro- and anti-tumorigenic phenotypes and may enhance or suppress tumor growth. Due to their tumor-homing properties, MSCs and their exosomes may be used as vehicles for delivering anti-tumorigenic agents in tumor cells, attenuating their viability and invasive characteristics. Since many factors affect the phenotype and function of MSCs in the tumor microenvironment, a better understanding of signaling pathways that regulate the cross-talk between MSCs, immune cells and tumor cells will pave the way for the clinical use of MSCs in cancer immunotherapy. In this review article, we summarize current knowledge on the molecular and cellular mechanisms that are responsible for the MSC-dependent modulation of the anti-tumor immune response and we discuss different insights regarding therapeutic potential of MSCs in the therapy of malignant diseases.