scholarly journals Cell biobank as a necessary infrastructure for the development and implementation of mesenchymal stem cell-based therapy in the treatment of anthracycline-induced cardiotoxicity. Literature review and own data

2020 ◽  
Vol 19 (6) ◽  
pp. 2733
Author(s):  
L. Yu. Grivtsova ◽  
O. E. Popovkina ◽  
N. N. Dukhova ◽  
O. A. Politiko ◽  
V. V. Yuzhakov ◽  
...  

Cardiovascular diseases, along with cancer, are the leading causes of death worldwide. Although modern pharmacological treatment of various cardiomyopathies can slow the development of myocardial dysfunction, they have limited effectiveness in patients with end-stage disease. Many researchers believe that heart transplantation is the only radical treatment in this case. However, the lack of donors and the high operation cost require careful selection of surgical candidates. With the introduction of molecular and cell biology into medical practice, today, stem cell therapy can become an alternative method of nonsurgical restoration of myocardial functions. The most studied and attractive is the use of mesenchymal stem cells (MSCs). MSCs differ from hematopoietic stem cells used as support for hematopoiesis in high-dose chemotherapy by the following features: pronounced trophic effect, immune tolerance, the ability to suppress alloreactivity and autoimmune disorders. An important stage in the implementation of cell therapy is the creation of a cell biobank of MSCs. In A.F.Tsyb Medical Radiological Research Center, this work has been carried out since1984. Asignificant number of experimental studies have been carried out, confirming the possibility of clinical implementation of this approach. A method for obtaining stable cultures of MSCs and cardiomyoblasts from bone marrow cells was developed and approvals were obtained. Experimental studies of cell therapy are also being conducted to overcome anthracycline-induced cardiotoxicity in cancer patients.This article is devoted to practical application of MSC-based therapy, in particular, in cancer patients with cardiotoxicity, as well as to the issues of creating a cell biobank for treatment with MSCs.

2011 ◽  
Vol 300 (5) ◽  
pp. G684-G696 ◽  
Author(s):  
R. C. Mifflin ◽  
I. V. Pinchuk ◽  
J. I. Saada ◽  
D. W. Powell

The subepithelial intestinal myofibroblast is an important cell orchestrating many diverse functions in the intestine and is involved in growth and repair, tumorigenesis, inflammation, and fibrosis. The myofibroblast is but one of several α-smooth muscle actin-positive (α-SMA+) mesenchymal cells present within the intestinal lamina propria, including vascular pericytes, bone marrow-derived stem cells (mesenchymal stem cells or hematopoietic stem cells), muscularis mucosae, and the lymphatic pericytes (colon) and organized smooth muscle (small intestine) associated with the lymphatic lacteals. These other mesenchymal cells perform many of the functions previously attributed to subepithelial myofibroblasts. This review discusses the definition of a myofibroblast and reconsiders whether the α-SMA+ subepithelial cells in the intestine are myofibroblasts or other types of mesenchymal cells, i.e., pericytes. Current information about specific, or not so specific, molecular markers of lamina propria mesenchymal cells is reviewed, as well as the origins of intestinal myofibroblasts and pericytes in the intestinal lamina propria and their replenishment after injury. Current concepts and research on stem cell therapy for intestinal inflammation are summarized. Information about the stem cell origin of intestinal stromal cells may inform future stem cell therapies to treat human inflammatory bowel disease (IBD).


Blood ◽  
2000 ◽  
Vol 96 (13) ◽  
pp. 4185-4193 ◽  
Author(s):  
Hanno Glimm ◽  
IL-Hoan Oh ◽  
Connie J. Eaves

Abstract An understanding of mechanisms regulating hematopoietic stem cell engraftment is of pivotal importance to the clinical use of cultured and genetically modified transplants. Human cord blood (CB) cells with lymphomyeloid repopulating activity in NOD/SCID mice were recently shown to undergo multiple self-renewal divisions within 6 days in serum-free cultures containing Flt3-ligand, Steel factor, interleukin 3 (IL-3), IL-6, and granulocyte colony-stimulating factor. The present study shows that, on the fifth day, the transplantable stem cell activity is restricted to the G1fraction, even though both colony-forming cells (CFCs) and long-term culture-initiating cells (LTC-ICs) in the same cultures are approximately equally distributed between G0/G1and S/G2/M. Interestingly, the G0 cells defined by their low levels of Hoechst 33342 and Pyronin Y staining, and reduced Ki67 and cyclin D expression (representing 21% of the cultured CB population) include some mature erythroid CFCs but very few primitive CFCs, LTC-ICs, or repopulating cells. Although these findings suggest a cell cycle–associated change in in vivo stem cell homing, the cultured G0/G1 and S/G2/M CD34+ CB cells exhibited no differences in levels of expression of VLA-4, VLA-5, or CXCR-4. Moreover, further incubation of these cells for 1 day in the presence of a concentration of transforming growth factor β1 that increased the G0/G1 fraction did not enhance detection of repopulating cells. The demonstration of a cell cycle–associated mechanism that selectively silences the transplantability of proliferating human hematopoietic stem cells poses both challenges and opportunities for the future improvement of ex vivo–manipulated grafts.


Blood ◽  
2000 ◽  
Vol 96 (13) ◽  
pp. 4185-4193 ◽  
Author(s):  
Hanno Glimm ◽  
IL-Hoan Oh ◽  
Connie J. Eaves

An understanding of mechanisms regulating hematopoietic stem cell engraftment is of pivotal importance to the clinical use of cultured and genetically modified transplants. Human cord blood (CB) cells with lymphomyeloid repopulating activity in NOD/SCID mice were recently shown to undergo multiple self-renewal divisions within 6 days in serum-free cultures containing Flt3-ligand, Steel factor, interleukin 3 (IL-3), IL-6, and granulocyte colony-stimulating factor. The present study shows that, on the fifth day, the transplantable stem cell activity is restricted to the G1fraction, even though both colony-forming cells (CFCs) and long-term culture-initiating cells (LTC-ICs) in the same cultures are approximately equally distributed between G0/G1and S/G2/M. Interestingly, the G0 cells defined by their low levels of Hoechst 33342 and Pyronin Y staining, and reduced Ki67 and cyclin D expression (representing 21% of the cultured CB population) include some mature erythroid CFCs but very few primitive CFCs, LTC-ICs, or repopulating cells. Although these findings suggest a cell cycle–associated change in in vivo stem cell homing, the cultured G0/G1 and S/G2/M CD34+ CB cells exhibited no differences in levels of expression of VLA-4, VLA-5, or CXCR-4. Moreover, further incubation of these cells for 1 day in the presence of a concentration of transforming growth factor β1 that increased the G0/G1 fraction did not enhance detection of repopulating cells. The demonstration of a cell cycle–associated mechanism that selectively silences the transplantability of proliferating human hematopoietic stem cells poses both challenges and opportunities for the future improvement of ex vivo–manipulated grafts.


Author(s):  
Nursuaidah Abdullah ◽  
Marjanu Hikmah Elias

Type 1 diabetes (T1D) is a deficiency in insulin production which is mainly due to loss of ?-cell pancreatic islets. Patients with T1D need to be given exogenous insulin regularly. While improvements in the delivery of insulin and glucose monitoring methods have been effective in improving patient safety, insulin therapy is not a cure and is often associated with complications and debilitating hypoglycaemic episodes. Meanwhile, pancreas or islet transplantation as a gold standard only promises temporary freedom from exogenous insulin and suffers from issues of its own. Stem cell therapy may provide a more permanent solution, given stem cells’ immunomodulatory characteristics and ability to self-renew and distinguish into specific cells. In this sense, the therapeutic potentials of stem cells are addressed in this study. These stem cells cover a wide range of treatments for T1D including embryonic stem cells, induced pluripotent stem cells, bone-marrow derived hematopoietic stem cells and multipotent mesenchymal stromal cells. The challenges faced by the current stem cell transplant in T1D treatment and Islamic viewpoints regarding ethics in stem cell research and therapy are also discussed. In conclusion, stem cell therapy offers a safe and efficient alternative treatment for T1D. However, besides the fatwa from Fatwa Committee of Selangor, the lack of Malaysian stem cells ethics should be further addressed.


Stroke ◽  
2020 ◽  
Vol 51 (9) ◽  
pp. 2854-2862 ◽  
Author(s):  
You Jeong Park ◽  
Kuniyasu Niizuma ◽  
Maxim Mokin ◽  
Mari Dezawa ◽  
Cesar V. Borlongan

Stem cell-based regenerative therapies may rescue the central nervous system following ischemic stroke. Mesenchymal stem cells exhibit promising regenerative capacity in in vitro studies but display little to no incorporation in host tissue after transplantation in in vivo models of stroke. Despite these limitations, clinical trials using mesenchymal stem cells have produced some functional benefits ascribed to their ability to modulate the host’s inflammatory response coupled with their robust safety profile. Regeneration of ischemic brain tissue using stem cells, however, remains elusive in humans. Multilineage-differentiating stress-enduring (Muse) cells are a distinct subset of mesenchymal stem cells found sporadically in connective tissue of nearly every organ. Since their discovery in 2010, these endogenous reparative stem cells have been investigated for their therapeutic potential against a variety of diseases, including acute myocardial infarction, stroke, chronic kidney disease, and liver disease. Preclinical studies have exemplified Muse cells’ unique ability mobilize, differentiate, and engraft into damaged host tissue. Intravenously transplanted Muse cells in mouse lacunar stroke models afforded functional recovery and long-term engraftment into the host neural network. This mini-review article highlights these biological properties that make Muse cells an exceptional candidate donor source for cell therapy in ischemic stroke. Elucidating the mechanism behind the therapeutic potential of Muse cells will undoubtedly help optimize stem cell therapy for stroke and advance the field of regenerative medicine.


2020 ◽  
Vol 10 (14) ◽  
pp. 4852 ◽  
Author(s):  
Shima Masoudi Asil ◽  
Jyoti Ahlawat ◽  
Gileydis Guillama Barroso ◽  
Mahesh Narayan

In addition to adverse health outcomes, neurological disorders have serious societal and economic impacts on patients, their family and society as a whole. There is no definite treatment for these disorders, and current available drugs only slow down the progression of the disease. In recent years, application of stem cells has been widely advanced due to their potential of self-renewal and differentiation to different cell types which make them suitable candidates for cell therapy. In particular, this approach offers great opportunities for the treatment of neurodegenerative disorders. However, some major issues related to stem-cell therapy, including their tumorigenicity, viability, safety, metastases, uncontrolled differentiation and possible immune response have limited their application in clinical scales. To address these challenges, a combination of stem-cell therapy with nanotechnology can be a solution. Nanotechnology has the potential of improvement of stem-cell therapy by providing ideal substrates for large scale proliferation of stem cells. Application of nanomaterial in stem-cell culture will be also beneficial to modulation of stem-cell differentiation using nanomedicines. Nanodelivery of functional compounds can enhance the efficiency of neuron therapy by stem cells and development of nanobased techniques for real-time, accurate and long-lasting imaging of stem-cell cycle processes. However, these novel techniques need to be investigated to optimize their efficiency in treatment of neurologic diseases.


2021 ◽  
Vol 19 ◽  
Author(s):  
Maria Ejma ◽  
Natalia Madetko ◽  
Anna Brzecka ◽  
Piotr Alster ◽  
Sławomir Budrewicz ◽  
...  

Background: Stroke is a major challenge in neurology due to its multifactorial genesis and irreversible consequences. Processes of endogenous post-stroke neurogenesis, although insufficient, may indicate possible direction of future therapy. Multiple research considers stem-cell-based approaches in order to maximize neuroregeneration and minimize post-stroke deficits. Objective: Aim of this study is to review current literature considering post-stroke stem-cell- based therapy and possibilities of inducing neuroregeneration after brain vascular damage. Methods: Papers included in this article were obtained from PubMed and MEDLINE databases. The following medical subject headings (MeSH) were used: “stem cell therapy”, “post-stroke neurogenesis”, “stem-cells stroke”, “stroke neurogenesis”, “stroke stem cells”, “stroke”, “cell therapy”, “neuroregeneration”, “neurogenesis”, “stem-cell human”, “cell therapy in human”. Ultimate inclusion was made after manual review of the obtained reference list. Results: Attempts of stimulating neuroregeneration after stroke found in current literature include supporting endogenous neurogenesis, different routes of exogenous stem cells supplying and extracellular vesicles used as a method of particle transport. Conclusion: Although further research in this field is required, post stroke brain recovery supported by exogenous stem cells seems to be promising future therapy revolutionizing modern neurology.


2017 ◽  
Vol 2017 ◽  
pp. 1-13 ◽  
Author(s):  
Carine Ghem ◽  
Lucinara Dadda Dias ◽  
Roberto Tofani Sant’Anna ◽  
Renato A. K. Kalil ◽  
Melissa Markoski ◽  
...  

Clinical trials using stem cell therapy for heart diseases have not reproduced the initial positive results obtained with animal models. This might be explained by a decreased regenerative capacity of stem cells collected from the patients. This work aimed at the simultaneous investigation of endothelial stem/progenitor cells (EPCs), mesenchymal stem/progenitor cells (MSCs), and hematopoietic stem/progenitor cells (HSCs) in sternal bone marrow samples of patients with ischemic or valvular heart disease, using flow cytometry and colony assays. The study included 36 patients referred for coronary artery bypass grafting or valve replacement surgery. A decreased frequency of stem cells was observed in both groups of patients. Left ventricular dysfunction, diabetes, and intermediate risk in EuroSCORE and SYNTAX score were associated with lower EPCs frequency, and the use of aspirin andβ-blockers correlated with a higher frequency of HSCs and EPCs, respectively. Most importantly, the distribution of frequencies in the three stem cell compartments showed independent patterns. The combined investigation of the three stem cell compartments in patients with cardiovascular diseases showed that they are independently affected by the disease, suggesting the investigation of prognostic factors that may be used to determine when autologous stem cells may be used in cell therapy.


2021 ◽  
Vol 10 (3) ◽  
pp. 72-78
Author(s):  
P. M. Docshin ◽  
A. Bairqdar ◽  
A. B. Malashicheva

Modern methods of treating heart failure are similar to the palliative care, since they mostly relieve the symptoms of the disease. The discovery of resident cardiac stem cells gave impetus to the development of “second generation” cell therapy, which quickly moved from animal research to clinical trials with critically ill patients. Many cardiac side population cells have been identified to have stem cells characteristics and some additional individual characteristics, both in vitro and in vivo. The results of clinical studies demonstrated that the stem cell treatment is safe, however, this type of cell-based therapy did not restore cardiac function. Its effects were limited to mildly improving left ventricular systolic pressure and reducing the scar area. Despite that, the promising nature of these therapeutic approaches for heart diseases have contributed to the development of next-generation cell therapy.


2018 ◽  
Vol 87 (1) ◽  
pp. 1015-1027 ◽  
Author(s):  
Hans Clevers ◽  
Fiona M. Watt

Central to the classical hematopoietic stem cell (HSC) paradigm is the concept that the maintenance of blood cell numbers is exclusively executed by a discrete physical entity: the transplantable HSC. The HSC paradigm has served as a stereotypic template in stem cell biology, yet the search for rare, hardwired professional stem cells has remained futile in most other tissues. In a more open approach, the focus on the search for stem cells as a physical entity may need to be replaced by the search for stem cell function, operationally defined as the ability of an organ to replace lost cells. The nature of such a cell may be different under steady state conditions and during tissue repair. We discuss emerging examples including the renewal strategies of the skin, gut epithelium, liver, lung, and mammary gland in comparison with those of the hematopoietic system. While certain key housekeeping and developmental signaling pathways are shared between different stem cell systems, there may be no general, deeper principles underlying the renewal mechanisms of the various individual tissues.


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