JADICELL -Mesenchymal Stem Cells: A New Piece in the Puzzle of COVID-19 Treatment

curncman
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Re: JADICELL -Biomimetic microenvironmental preconditioning enhance neuroprotective properties of human mesenchymal stem

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Biomimetic microenvironmental preconditioning enhance neuroprotective properties of human mesenchymal stem cells derived from Wharton's Jelly (WJ-MSCs)

https://www.nature.com/articles/s41598-020-74066-0

Abstract
Tuning stem cells microenvironment in vitro may influence their regenerative properties. In this study Wharton's Jelly-derived mesenchymal stem cells (WJ-MSCs) were encapsulated in 3D hydrogels derived from human fibrin (FB) or platelet lysate (PL) and the oxygen level was adjusted to physiological normoxia (5% O2). The influence of the type of the scaffold and physiological normoxia conditions was tested on the WJ-MSCs' survivability, proliferation, migratory potential, the level of expression of selected trophic factors, cytokines, and neural markers. Encapsulated WJ-MSCs revealed high survivability, stable proliferation rate, and ability to migrate out of the hydrogel and the up-regulated expression of all tested factors, as well as the increased expression of neural differentiation markers. Physiological normoxia stimulated proliferation of encapsulated WJ-MSCs and significantly enhanced their neuronal, but not glial, differentiation. Ex vivo studies with indirect co-culture of organotypic hippocampal slices and cell-hydrogel bio-constructs revealed strong neuroprotective effect of WJ-MSCs against neuronal death in the CA1 region of the rat hippocampus. This effect was potentiated further by FB scaffolds under 5% O2 conditions. Our results indicating significant effect of oxygen and 3D cytoarchitecture suggest the urgent need for further optimization of the microenvironmental conditions to improve therapeutical competence of the WJ-MSCs population.

Introduction
Tissue engineering and regenerative medicine are currently vast and rapidly growing research fields. The intrinsic qualities of stem cells, including differentiation potential and self-renewal, make them a frontline source for the cell therapy1. However, protection of the transplanted cells from the host immunological attack and the modulation of their properties by in vitro preconditioning are the main issues to consider for successful treatment2,3. Thus, the next important step toward regenerative personalized medicine would be formation of biologically active bio-constructs: scaffolds populated by stem cells that could replace damaged tissue and become actively involved in the immunological defense system.

Decades of in vitro and in vivo experiments have shed a new light on diverse characteristics and biochemical pathways involved in actions of stem cells derived from different sources and populations. It has been proven that even stem cells isolated from the same source can behave differently if cultured under differing conditions4,5. Thus, in order to obtain therapeutically competent cell populations standardization of the in vitro culture in regard to recipient tissue requirements is necessary6.

In pursuit of the ultimate goal of developing artificial tissues similar to native ones, several preconditioning factors of stem cell culture were performed, including: reduced oxygen level (physiological normoxia) instead of commonly used atmospheric level (21% O2), optimal stem cell density, specific growth media composition, 3D versus 2D culture with different types of 3D scaffold itself. Taking together, they warrant the need for further evaluation5.

Mesenchymal stem/stromal cells (MSCs), a mesodermal population that can be derived from both adult and birth tissues, are currently the type of stem cells most widely used in clinical trials (www.clinicaltrials.gov)7. Loss of potency, inconsistent quality, the invasive nature of procedures used for cell isolation and time needed to expand cell culture severely, limit the use of classical source of MSCs such as bone marrow for many clinical applications. MSCs isolated from birth tissue display similar general characteristics of MSCs derived from adult tissue but exhibits higher proliferative potential and fewer signs of senescence as compared to MSCs obtained from other sources8. Wharton's Jelly (WJ), being rich in perinatal MSCs, is acquired from umbilical cord tissue that is typically disposed of as medical waste. Therefore, harvesting these cells does not pose any threat to the donor and incurs minimal costs.

Despite low immunogenicity and strong immunomodulatory properties mesenchymal stem cells derived from Wharton's Jelly (WJ-MSCs) display high capacity to spontaneously differentiate towards a neural lineage9. However source of stem cells, their isolation method4 and subsequent transplantation, can significantly affect their properties.

Recently, our research team demonstrated that mesenchymal stem cells derived from human Wharton's Jelly secreted plethora anti-inflammatory, anti-apoptotic, angiogenic, and neurogenic factors4,10. Basing on this data, WJ-MSCs were chosen for this study to repopulate biocompatible scaffolds and, further, to evaluate their therapeutic values in changeable biomimetic conditions in vitro.

Biomedical research combining stem cells and scaffold engineering requires multidisciplinary approaches that include biology and biotechnology to control cell distribution and dynamics of cell culture, as well as chemistry and physics, to construct the scaffold of required composition and cytoarchitecture. An abundance of different modalities led to some confusion concerning scaffold types and generations. Therefore, a very recent effort was made to regulate this field and categorize scaffolds in a seven-layer format11. Ideal scaffold should be biocompatible, biodegradable, stable, flexible mechanically, easy and inexpensive in production, non-toxic, and providing dynamic interactions that foster and regulate stem cells in a way that mimics naturally occurring events in a cellular microenvironment6,12. Regarding the tissue-engineering point of view, the goal of a scaffold is to successfully mimic the biology of the extracellular matrix (ECM) by providing a 3D microenvironment suitable for cell adhesion and proliferation under specific chemical and biophysical stimuli13.

However, when transition of stem-cell therapy from lab to bedside is required, the standardized, large-scale propagation of clinically relevant MSCs in an animal-serum-free medium is an essential factor profoundly defining the overall safety of stem cell therapies14.

Two scaffold types were used to encapsulate WJ-MSCs for this study. One type consisted of hydrogel made from human fibrin (FB), the other from human platelet lysate (PL).

Fibrin is a serum-derived protein which plays a vital role in process of coagulation. In order to stop bleeding, thrombin cleaves fibrinogen into fibrin monomers that assemble into a fibrous 3D network with the physical properties of soft tissue15. Recent research indicates that 3D fibrin scaffolds function as an efficient material facilitating process of engineering tissues obtained from pluripotent stem cells16. Moreover, it was demonstrated that embedding of neural stem cells in 3D fibrin scaffolds increase cellular survival and their further neuronal differentiation after transplantation into the injured spinal cord16. Unfortunately, fibrins' rapid degradation remains a major limitation for many tissue-engineering applications, as was shown in the process of supporting differentiation of human pluripotent stem cells17. Nevertheless, a recent discovery proved that fibrin gel obtained from cord blood is characterized by a specific protein profile that contributes to tissue regeneration, suggesting further study is warranted5.

Platelet lysate is currently under deep investigation as an innovative compound in the field of tissue repair and regeneration. In addition to effectively support MSCs culture, PL-based scaffold networks have been proven to enhance fibroblasts and endothelial cells adhesion and proliferation18. Additional advantages of PL-based scaffolds include its human origin and its uniquely intrinsic immunomodulatory properties. Recent research suggests PL-rich scaffolds do not change expression of surface markers on cultured cells18 and they reduce culture time by increasing growth rate of the cells. This type of the scaffold has also been found to effectively support cellular multilineage differentiation capacity of stem cells, thereby encouraging development of osteoblasts, chondrocytes, adipocytes, neurons, astrocytes, and other cell types19,20. These properties may prove to be of great value when designing 3D scaffolds to replace large tissue fragments21.

One must consider both the immunological properties of stem cells and scaffold endurance when developing a scaffold for transplant. For best results, bioconstruction should closely mimic the natural microenvironment of the highly specialized tissue at the target zone. To do so, three basic issues must be addressed: type of stem cells, type of scaffold biomaterial, and the most appropriate culture method.

Therefore, to find out and evaluate in vitro microenvironment supporting Wharton's Jelly-derived mesenchymal stem cells regenerative parameters, three-dimensional (3D) scaffolds based on human-derived proteins (i.e., platelet lysate or human plasma fibrinogen) were combined with the oxygen level adjusted to "physiological normoxia" in a chamber that provides constant culture conditions (Xvivo System, Biospherix).

This study indicates that physiological normoxia and 3D microenvironmental conditions induce positive neuroprotective and immunomodulatory response of WJ-MSCs in injured neuronal tissue, which is significantly different as compared to the control, 2D conditions. Furthermore, it highlights an urgent need to develop appropriate protocols for culturing, phenotypic verification, and biosafety control of acquired cells, as well as the protocols for enhancing therapeutic properties of transplanted cells and survival after transplantation. The proposed models of scaffolds/cell hybrids show promise of future use in MSCs-based therapy.
curncman
Posts: 496
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JADICELL -Mesenchymal stem cells reverse EMT process through blocking the activation of NF-κB and Hedgehog pathways in L

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Mesenchymal stem cells reverse EMT process through blocking the activation of NF-κB and Hedgehog pathways in LPS-induced acute lung injury

https://www.nature.com/articles/s41419-020-03034-3
curncman
Posts: 496
Joined: Fri Jun 26, 2020 8:27 am

MSC Rising Stars: Talking Stem Cell Potency and Aging with Rebekah Samsonraj

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MSC Rising Stars: Talking Stem Cell Potency and Aging with Rebekah Samsonraj

https://www.roosterbio.com/mscs-charact ... samsonraj/
curncman
Posts: 496
Joined: Fri Jun 26, 2020 8:27 am

A strategic collaboration to speed up the development of allogeneic cell therapies

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A strategic collaboration to speed up the development of allogeneic cell therapies

https://www.news-medical.net/amp/news/2 ... apies.aspx

The University of Texas MD Anderson Cancer Center and Allogene Therapeutics, Inc. today announced a strategic five-year collaboration agreement for the preclinical and clinical investigation of AlloCAR T candidates across Allogene's broad portfolio of hematologic and solid tumors.

MD Anderson's expertise in innovative clinical trials and well established translational research infrastructure will provide unique insights that will help expedite the development of AlloCAR T therapies. Coupled with Allogene's cell therapy expertise, we believe this institution-industry alliance could play an important role in bringing this next revolution in oncology treatment to patients."

Rafael Amado, M.D., Executive Vice President of Research and Development and Chief Medical Officer, Allogene
curncman
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JADICELL - Therapeutic potential of mesenchymal stem cells in treating both types of diabetes mellitus and associated di

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Therapeutic potential of mesenchymal stem cells in treating both types of diabetes mellitus and associated diseases
curncman
Posts: 496
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JADICELL Therapeutic potential of mesenchymal stem cells in treating both types of diabetes mellitus and associated dise

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Therapeutic potential of mesenchymal stem cells in treating both types of diabetes mellitus and associated diseases

https://link.springer.com/article/10.10 ... 20-00647-5

Abstract
Diabetes mellitus is a common lifestyle disease which can be classified into type 1 diabetes mellitus and type 2 diabetes mellitus. While both result in hyperglycemia due to lack of insulin action and further associated chronic ailments, there is a marked distinction in the cause for each type due to which both require a different prophylaxis. As observed, type 1 diabetes is caused due to the autoimmune action of the body resulting in the destruction of pancreatic islet cells. On the other hand, type 2 diabetes is caused either due to insulin resistance of target cells or lack of insulin production as per physiological requirements. Attempts to cure the disease have been made by bringing drastic changes in the patients’ lifestyle; parenteral administration of insulin; prescription of drugs such as biguanides, meglitinides, and amylin; pancreatic transplantation; and immunotherapy. While these attempts cause a certain degree of relief to the patient, none of these can cure diabetes mellitus. However, a new treatment strategy led by the discovery of mesenchymal stem cells and their unique immunomodulatory and multipotent properties has inspired therapies to treat diabetes by essentially reversing the conditions causing the disease. The current review aims to enumerate the role of various mesenchymal stem cells and the different approaches to treat both types of diabetes and its associated diseases as well.
curncman
Posts: 496
Joined: Fri Jun 26, 2020 8:27 am

JADICELL -Application of autologous endometrial mesenchymal stromal/stem cells increases thin endometrium receptivity: a

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Application of autologous endometrial mesenchymal stromal/stem cells increases thin endometrium receptivity: a case report

https://link.springer.com/article/10.11 ... 20-02515-5

Abstract
Background
Pregnancy in cycles with the use of assisted reproductive technologies is possible only with the availability of good-quality embryos and a healthy receptive endometrium. The problem of lack of sensitivity of the endometrium is related to the syndrome of thin endometrium, which is caused by a number of factors. However, there is no single protocol for the treatment of this syndrome, the return/improvement of normal functionality of endometrial tissue, and obtaining the desired pregnancy.

Case presentation
We report a case of a 38-year-old Ukrainian woman with a number of unsuccessful tries at pregnancy in cycles with the use of assisted reproductive technologies. We describe a clinical case of the use of mesenchymal stem cells of the human endometrium for a woman with thin endometrial syndrome to increase its receptivity for pregnancy. The basic steps of patient management, protocol of sampling material for obtaining a cell product based on endometrial stem cells, their basic morphofunctional characteristics, and post-treatment procedures to obtain the desired pregnancy are described.

Conclusion
Application of autologous endometrial mesenchymal stem cells increases endometrial receptivity and the chance for pregnancy with use of assisted reproductive technologies
curncman
Posts: 496
Joined: Fri Jun 26, 2020 8:27 am

JADICELL Global and Japan Human Mesenchymal Stem Cells (hMSC) Market

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Global and Japan Human Mesenchymal Stem Cells (hMSC) Market


https://www.prnewsprime.com/2020/10/glo ... sc-market/

Global Human Mesenchymal Stem Cells (hMSC) Scope and Market Size
Human Mesenchymal Stem Cells (hMSC) market is segmented by Type, and by Application. Players, stakeholders, and other participants in the global Human Mesenchymal Stem Cells (hMSC) market will be able to gain the upper hand as they use the report as a powerful resource. The segmental analysis focuses on revenue and forecast by Type and by Application in terms of revenue and forecast for the period 2015-2026.

Market segment by Type, the product can be split into

Umbilical Cord Matrix hMSC
Bone Marrow hMSC
Adipose Tissue hMSC
Other
Market segment by Application, split into

Medical Application
Research
Other Applications
curncman
Posts: 496
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JADICELL -Circular RNA 0001273 in exosomes derived from human umbilical cord mesenchymal stem cells (UMSCs) in myocardia

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Circular RNA 0001273 in exosomes derived from human umbilical cord mesenchymal stem cells (UMSCs) in myocardial infarction

https://www.europeanreview.org/article/23228

Circular RNA 0001273 in exosomes derived from human umbilical cord mesenchymal stem cells (UMSCs) in myocardial infarction
C.-X. Li, J. Song, X. Li, T. Zhang, Z.-M. Li

Department of Cardiology, Qingdao Central Hospital, Qingdao, China. 12124861@cumt.edu.cn

CARDIOLOGY
OBJECTIVE: To investigate whether human umbilical cord mesenchymal stem cells (UMSCs) derived exosomes (exosome) can repair the heart after myocardial infarction (MI) by delivering circ-0001273 and its mechanism.

MATERIALS AND METHODS: Through the Sprague Dawley (SD) rat MI model was established, at the same time, we designed si-circ-0001273. Phosphate-buffered saline (PBS), exosome and si-circ-0001273-exosome were transplanted into ischemic hearts of rat, respectively. Through the echocardiography, hematoxylin-eosin staining (HE) method to detect the rat heart recovery. Meanwhile, H9c2 was treated with hypoxic serum-free serum to construct an in vitro apoptosis model to further explore the effect of circ-0001273 on myocardial cell apoptosis.

RESULTS: Compared with the exosome-treated group, the left ventricular ejection fraction (EF) and shortened fraction (FS) of the rat heart was remarkably reduced and the cardiac structure was more disordered in the si-circ-0001273-exosome-treated group. Meanwhile, in vitro TUNEL staining and flow cytometry detection, results showed that compared with the exosome co-culture group, the incidence of H9C2 cell apoptosis in the si-circ-0001273-exosome co-culture group was obviously increased.

CONCLUSIONS: Circ-0001273 can remarkably inhibit the occurrence of myocardial cell apoptosis in ischemic environment, promote MI repair, and provide a good reference for clinical treatment.
curncman
Posts: 496
Joined: Fri Jun 26, 2020 8:27 am

JADICELL -Mesenchymal Stem Cells: A New Piece in the Puzzle of COVID-19 Treatment

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https://imms.kz/?q=en/news/682
Stem cells are cell factories that continually divide to create new cells. Implanting stem cells into damaged organs can regenerate new tissue.



The joint research team significantly reduced the total harvesting period of the stem cell leaf to two days. Nanotopography of poly (N-isopropylacrylamide) (PNIPAAm), which sharply changes its roughness with temperature, allows the collection of cell layers consisting of mesenchymal stem cells derived from bone marrow.



The research focused on converting stem cells into sheets in a short time to increase their beneficial properties. The team achieved this by applying an isotropic pattern of 400 nm nanopores to the surface of a 3D 3D PNIPAAm. As a result, not only the formation and maturation of mesenchymal stem cells derived from human bone marrow was accelerated, but also the surface roughness of the bulk PNIPAAm at room temperature below the lower critical mark was rapidly reduced, effectively inducing detachment of cell sheets, which, in turn, made it possible to quickly collect the sheets. mesenchymal stem cells from human bone marrow.



“We have significantly reduced the collection time by introducing nanotopography onto the surface of the 3D 3D PNIPAAm. As a result, sheets of mature stem cells were obtained for the first time in the world. We have the opportunity to apply the sheets directly to patients in the future, ”added the researchers.
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