Stem cells as a promising therapeutic direction for the treatment of serious diseases

Medical Centers ◽

Modern Methods ◽

The Usa ◽

Biological Plasticity ◽

The U.S

ABSTRACT. Stem cells have attracted scientific, clinical and public interest because they can regenerate and develop in certain types of cells, depending on their source of origin and biological plasticity. Several strategies for the use of cell therapy are currently being explored. A total of 8357 clinical trials of various stages using stem cells have been registered. The possibility of using multipotent mesenchymal stromal cells in patients with COVID-19-induced complications is being actively investigated. However, among the stem cell products, the U.S. Food and Drug Administration (FDA) has so far approved only those that are produced from umbilical cord blood. In the USA and European countries, there are private clinics that provide services for the collection and cultivation of stem cells, mainly autologous. Such medical centers can become the point of concentration of personalized medicine, focused on the needs of a particular patient and his/her possibilities of receiving targeted therapy for severe, difficult-to-treat conditions using modern methods in cellular technologies. The article presents an analysis of existing strategies for the therapeutic use of stem cells and the most promising directions for their further study.

From mesenchymal stem cells and stromal cells - from bench to bedside

Trillium Exctracellular Vesicles ◽

10.47184/tev.2019.01.05 ◽

2019 ◽

Vol 1 (1) ◽

pp. 36-39

Author(s):

Bernd Giebel ◽

Verena Börger ◽

Mario Gimona ◽

Eva Rohde

Keyword(s):

Stem Cells ◽

Clinical Trials ◽

Mesenchymal Stem Cells ◽

Stromal Cells ◽

Therapeutic Agent ◽

Therapeutic Potential ◽

Therapeutic Effects ◽

Cell Replacement ◽

Beneficial Effects ◽

Promising Tool

Human mesenchymal stem/stromal cells (MSCs) represent a promising tool in regenerative medicine. Until now, almost one thousand NIH-registered clinical trials investigated their immunomodulatory and pro-regenerative therapeutic potential in various diseases. Despite controversial reports regarding the efficacy of MSC-treatments, MSCs appear to exert their beneficial effects in a paracrine manner rather than by cell replacement. In this context, extracellular vesicles (EVs), such as exosomes and microvesicles, seem to induce the MSCs’ therapeutic effects. Here, we briefly illustrate the potential of MSC-EVs as therapeutic agent of the future.

Neural differentiation of canine mesenchymal stem cells/multipotent mesenchymal stromal cells

BMC Veterinary Research ◽

10.1186/s12917-020-02493-2 ◽

2020 ◽

Vol 16 (1) ◽

Author(s):

Sonja Prpar Mihevc ◽

Vesna Kokondoska Grgich ◽

Andreja Nataša Kopitar ◽

Luka Mohorič ◽

Gregor Majdič

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Multipotent Mesenchymal Stromal Cells

Stromal Cells ◽

Neural Differentiation ◽

Silk fibroin induces chondrogenic differentiation of canine adipose–derived multipotent mesenchymal stromal cells/mesenchymal stem cells

Journal of Tissue Engineering ◽

10.1177/2041731419835056 ◽

2019 ◽

Vol 10 ◽

pp. 204173141983505 ◽

Cited By ~ 5

Author(s):

Metka Voga ◽

Natasa Drnovsek ◽

Sasa Novak ◽

Gregor Majdic

Keyword(s):

Stem Cells ◽

Cell Culture ◽

Stromal Cells ◽

Chondrogenic Differentiation ◽

Culture Medium ◽

Collagen Type ◽

Culture Conditions ◽

Standard Cell ◽

Cell Culture Medium

Under appropriate culture conditions, mesenchymal stem cells (MSC), also called more properly multipotent mesenchymal stromal cells (MMSC), can be induced toward differentiation into different cell lineages. In order to guide stem cell fate within an environment resembling the stem cell niche, different biomaterials are being developed. In the present study, we used silk fibroin (SF) as a biomaterial supporting the growth of MMSC and studied its effect on chondrogenesis of canine adipose–derived MMSC (cADMMSC). Adipose tissue was collected from nine privately owned dogs. MMSC were cultured on SF films and SF scaffolds in a standard cell culture medium. Cell morphology was evaluated by scanning electron microscopy (SEM). Chondrogenic differentiation was evaluated by alcian blue staining and mRNA expression of collagen type 1, collagen type 2, Sox9, and Aggrecan genes. cADMMSC cultured on SF films and SF scaffolds stained positive using alcian blue. SEM images revealed nodule-like structures with matrix vesicles and fibers resembling chondrogenic nodules. Gene expression of chondrogenic markers Sox9 and Aggrecan were statistically significantly upregulated in cADMMSC cultured on SF films in comparison to negative control cADMMSC. This result suggests that chondrogenesis of cADMMSC could occur when cells were grown on SF films in a standard cell culture medium without specific culture conditions, which were previously considered necessary for induction of chondrogenic differentiation.

In Vitro Characterization of Multipotent Mesenchymal Stromal Cells Isolated from Palatal Subepithelial Tissue Grafts

Microscopy and Microanalysis ◽

10.1017/s143192761201433x ◽

2013 ◽

Vol 19 (2) ◽

pp. 370-380 ◽

Cited By ~ 13

Author(s):

Alexandra Roman ◽

Andrada Şoancă ◽

Adrian Florea ◽

Emőke Páll

Keyword(s):

Stem Cells ◽

Stromal Cells ◽

Embryoid Body ◽

Basic Research ◽

Positive Staining ◽

Basic Characteristics ◽

Tissue Grafts

AbstractThe aim of this study was to analyze whether the mesenchymal stromal cells (MSCs) isolated from palatal tissue grafts harvested in order to cover gingival recessions have the basic characteristics of stem cells. The palatal tissue cells were processed using a special culture medium that stimulated the development of only undifferentiated cellular lines. Cells at passage 4 were evaluated by flow cytometry to examine the expression of specific surface markers and were tested for multilineage differentiation capacity. These cells collected at passage 4 were also investigated for the capacity to cluster into embryoid body aggregates. Palatal MSCs displayed positive staining for the mesenchymal markers CD29, CD73, CD105, CD 49e, and CD44, but did not express hematopoietic markers CD34/45. The palatal MSCs successfully differentiated into osteogenic, adipogenic, and chondrogenic lineages. When seeded in special conditions, palatal MSCs propagated into unattached spheres resembling embryoid body aggregates consisting both of differentiated and undifferentiated cells as revealed at the ultrastructural evaluation. It is concluded that the isolated palatal MSCs fulfilled the basic criteria defining the stem cells. This new source of stem cells characterized here for the first time opens new perspectives on possible applications in basic research and in regenerative medicine.

Immunological Characterization Of Multipotent Mesenchymal Stromal Cells. The International Society For Cellular Therapy (ISCT) Working Proposal

Blood ◽

10.1182/blood.v122.21.5438.5438 ◽

2013 ◽

Vol 122 (21) ◽

pp. 5438-5438

Author(s):

Mauro Krampera ◽

Jacques Galipeau ◽

Yufang Shi ◽

Karin Tarte ◽

Luc Sensebé

Keyword(s):

Clinical Trials ◽

International Society ◽

Stromal Cells ◽

Quantitative Methods ◽

In Vivo Models ◽

Immunological Characterization

Abstract The large number of experimental approaches, culture conditions, qualitative and quantitative methods, and in vitro and in vivo models employed so far to assess immune regulatory properties of multipotent mesenchymal stromal cells (MSC) has led to an excess of literature data that sometimes are poorly comparable, redundant, and even contradictory. Thus, quite paradoxically, the risk is that pre-clinical literature data may become eventually weak and scarcely useful, in both researchers’ and Regulatory Authorities’ opinion, for supporting experimentally specific MSC-based clinical trials aimed at treating autoimmune and inflammatory diseases. However, some data in this field appear more solid and reproducible and may be generally accepted to suggest reproducible immunological assays to quantify the differences in immune modulatory properties of MSCs produced according to Good Manufacturing Practice (GMP). The MSC Committee of the International Society of Cell Therapy (ISCT) released a statement paper in 2006 that established the minimal criteria characterizing human MSC, without focusing particularly on their immunological properties. In the 7 years following the publication of this statement paper, more than 10,000 manuscripts on MSC, and many of them deal with immune regulation. To consolidate the scientific research in this field, the MSC Committee of the ISCT is publishing a working proposal paper aimed at stimulating the general discussion about the need of shared guidelines for the immunological characterization of MSCs for clinical use: 1. A standard immune plasticity assay should be implemented by using IFN-γ + TNF-α as model in vitro priming agent 2. Functional analysis of an expanded cell product may provide mechanistic insights on intra- and inter- study variance in clinical response amongst patients 3. The use of purified responders would be widely practicable and should provide more generalizable guidance on relative functional potency of MSC and as a companion to clinical trials 4. Interrogating the IDO response as part of an in vitro licensing assay should be considered central 5. Conclusions based on xenorecipient animal models on how to conduct clinical trials should be drawn with caution 6. The prospective hypothesis-driven analysis of lymphocyte populations in patients groups treated with MSC should be encouraged 7. Clinical analysis should also include the monitoring of whether injected MSCs are the target of an immune response. Disclosures: No relevant conflicts of interest to declare.

Heterogeneity of Multipotent Mesenchymal Stromal Cells: From Stromal Cells to Stem Cells and Vice Versa

Transplantation Journal ◽

10.1097/tp.0b013e3181a283ee ◽

2009 ◽

Vol 87 (Supplement) ◽

pp. S36-S42 ◽

Cited By ~ 48

Author(s):

Massimo Dominici ◽

Paolo Paolucci ◽

Pierfranco Conte ◽

Edwin M. Horwitz

Keyword(s):

Stem Cells ◽

Multipotent Mesenchymal Stromal Cells

Stromal Cells ◽

Challenges and advances in clinical applications of mesenchymal stromal cells

Journal of Hematology & Oncology ◽

10.1186/s13045-021-01037-x ◽

2021 ◽

Vol 14 (1) ◽

Author(s):

Tian Zhou ◽

Zenan Yuan ◽

Jianyu Weng ◽

Duanqing Pei ◽

Xin Du ◽

...

Keyword(s):

Stem Cells ◽

Clinical Trials ◽

Mesenchymal Stem Cells ◽

Stromal Cells ◽

Therapeutic Potential ◽

Clinical Applications ◽

Disease Models ◽

Animal Disease ◽

Animal Disease Models

AbstractMesenchymal stromal cells (MSCs), also known as mesenchymal stem cells, have been intensely investigated for clinical applications within the last decades. However, the majority of registered clinical trials applying MSC therapy for diverse human diseases have fallen short of expectations, despite the encouraging pre-clinical outcomes in varied animal disease models. This can be attributable to inconsistent criteria for MSCs identity across studies and their inherited heterogeneity. Nowadays, with the emergence of advanced biological techniques and substantial improvements in bio-engineered materials, strategies have been developed to overcome clinical challenges in MSC application. Here in this review, we will discuss the major challenges of MSC therapies in clinical application, the factors impacting the diversity of MSCs, the potential approaches that modify MSC products with the highest therapeutic potential, and finally the usage of MSCs for COVID-19 pandemic disease.

Mesenchymal stem Cells as a Treatment Strategy for Coronavirus Disease 2019 (COVID-19): Need for Authority Regulations and Clinical Guidelines

Current Stem Cell Research & Therapy ◽

10.2174/1574888x16999201124224816 ◽

2020 ◽

Vol 16 ◽

Author(s):

Ahmet Cevik Tufan

Keyword(s):

Stem Cells ◽

Clinical Trials ◽

Mesenchymal Stem Cells ◽

Severe Acute Respiratory Syndrome ◽

Extracellular Vesicles ◽

Stromal Cells ◽

Treatment Strategy ◽

Clinical Guidelines ◽

Treatment Strategies ◽

Recent Developments

Abstract:: The cause of coronavirus disease 2019 (COVID-19) known as the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, formerly designated 2019-nCoV) was first discovered in December 2019 in Wuhan, China. It then spread rapidly worldwide. Investigation for discovery of drugs to cure this disease continues. The currently accepted treatments are supportive but there is no specific disease curing intervention found yet. Since mid-February, therapies involving mesenchymal stem/stromal cells (MSCs) have been proposed for the treatment of patients with COVID-19. In light of these recent developments this review will focus on: i) the mechanism of SARS-CoV-2 action and the subsequent pathology in COVID-19, ii) the proposed mechanism(s) of outcome-improving action of MSCs or MSC-derived extracellular vesicles in COVID-19 pneumonia, iii) registered MSC-based clinical trials and interventions for the treatment of COVID-19, iv) published case studies/series/trials reporting the use of MSC-based treatments in COVID-19 cases, and finally v) the need for authority regulations and clinical guidelines for MSC-based treatment strategies for COVID-19.

Neural differentiation of canine mesenchymal stem cells/multipotent mesenchymal stromal cells

10.21203/rs.2.14063/v2 ◽

2020 ◽

Author(s):

Sonja Prpar Mihevc ◽

Vesna Kokondoska Grgich ◽

Andreja Nataša Kopitar ◽

Luka Mohorič ◽

Gregor Majdic

Keyword(s):

Stem Cells ◽

Flow Cytometry ◽

Mesenchymal Stem Cells ◽

Glial Cells ◽

Stromal Cells ◽

Neural Differentiation ◽

Neural Induction ◽

Induction Medium ◽

Neuronal Markers

Abstract Background: Ability of adipose tissue-derived multipotent mesenchymal stromal cells/mesenchymal stem cells (ASCs) to differentiate in neural lineages promises progress in the field of regenerative medicine especially for replacing damaged neuronal tissue in different neurological disorders. Reprogramming of ASCs can be induced by supplying growth medium with chemical neurogenic inductors and/or specific growth factors. We investigated the neural differentiation potential of canine ASCs using several growth media (KEM, NIMa, NIMb, NIMc) containing various combinations of neurogenic inductors: B27 supplement, valproic acid, forskolin, N2-supplement and retinoic acid. First the cells were preconditioned in proliferation medium, followed by induction of neuronal differentiation. Six canine ASCs cell lines were assessed, half from female and half from male donors. The cell morphology, growth dynamics, viability were observed along with expression of neuron and astrocyte specific markers, which were assessed by immunocytochemistry and flow cytometry. Results: After 3, 6 and 9 days, elongated neural-like cells with bipolar elongations were observed and some oval cells with light nuclei appeared. After three and nine days of neural induction, differentiation into neurons and glial cells was observed. Expression of neuronal markers tubulin beta III (TUBB3), neurofilament H (NF-H) and glial fibrillary acidic protein (GFAP) was observed by immunocytochemistry. High GFAP expression (between 70 and 90% of all cells) was detected after three days of growth in neural induction medium a (NIMa) by flow cytometry, and expression of adult neuronal markers NF-H and microtubule associated protein-2 (MAP2) was detected in around 25% of cells. After nine days of ASCs differentiation a drop in expression rates of all markers was detected. There were no differences between neural differentiation of ASCs isolated from female or male dogs. Conclusions: The differentiation repertoire of canine ASCs extends beyond mesodermal lineages. Using a defined neural induction medium the canine ASCs were able to transform to neural lineages, bearing markers of neuronal and glial cells and also displayed the typical neuronal morphology. Differentiated ASCs can be a source of neural cellular lineages for regenerative therapy of nerve damage and also could be applicable for modeling of neurodegenerative diseases.

Herb-Derived Products: Natural Tools to Delay and Counteract Stem Cell Senescence

Stem Cells International ◽

10.1155/2020/8827038 ◽

2020 ◽

Vol 2020 ◽

pp. 1-28

Author(s):

Provvidenza M. Abruzzo ◽

Silvia Canaider ◽

Valeria Pizzuti ◽

Luca Pampanella ◽

Raffaella Casadei ◽

...

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Stromal Cells ◽

Cell Senescence ◽

Self Renewal ◽

Diminished Capacity ◽

Age Related ◽

Secretory Phenotype

Cellular senescence plays a very important role in organismal aging increasing with age and in age-related diseases (ARDs). This process involves physiological, structural, biochemical, and molecular changes of cells, leading to a characteristic trait referred to “senescence-associated secretory phenotype (SASP).” In particular, with aging, stem cells (SCs) in situ exhibit a diminished capacity of self-renewal and show a decline in their functionality. The identification of interventions able to prevent the accumulation of senescent SCs in the organism or to pretreat cultured multipotent mesenchymal stromal cells (MSCs) prior to employing them for cell therapy is a main purpose of medical research. Many approaches have been investigated and resulted effective to prevent or counteract SC senescence in humans, as well as other animal models. In this work, we have reviewed the chance of using a number of herb-derived products as novel tools in the treatment of cell senescence, highlighting the efficacy of these agents, often still far from being clearly understood.