scholarly journals Dynamical Simulation of Effective Stem Cell Transplantation for Modulation of Microglia Responses in Stroke Treatment

Symmetry ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 404
Author(s):  
Awatif Jahman Alqarni ◽  
Azmin Sham Rambely ◽  
Ishak Hashim

Stem cell transplantation therapy may inhibit inflammation during stroke and increase the presence of healthy cells in the brain. The novelty of this work, is to introduce a new mathematical model of stem cells transplanted to treat stroke. This manuscript studies the stability of the mathematical model by using the current biological information on stem cell therapy as a possible treatment for inflammation from microglia during stroke. The model is proposed to represent the dynamics of various immune brain cells (resting microglia, pro-inflammation microglia, and anti-inflammation microglia), brain tissue damage and stem cells transplanted. This model is based on a set of five ordinary differential equations and explores the beneficial effects of stem cells transplanted at early stages of inflammation during stroke. The Runge–Kutta method is used to discuss the model analytically and solve it numerically. The results of our simulations are qualitatively consistent with those observed in experiments in vivo, suggesting that the transplanted stem cells could contribute to the increase in the rate of ant-inflammatory microglia and decrease the damage from pro-inflammatory microglia. It is found from the analysis and simulation results that stem cell transplantation can help stroke patients by modulation of the immune response during a stroke and decrease the damage on the brain. In conclusion, this approach may increase the contributions of stem cells transplanted during inflammation therapy in stroke and help to study various therapeutic strategies for stem cells to reduce stroke damage at the early stages.

Biomolecules ◽  
2021 ◽  
Vol 11 (9) ◽  
pp. 1316
Author(s):  
Reed Berlet ◽  
Stefan Anthony ◽  
Beverly Brooks ◽  
Zhen-Jie Wang ◽  
Nadia Sadanandan ◽  
...  

Stem cell transplantation with rehabilitation therapy presents an effective stroke treatment. Here, we discuss current breakthroughs in stem cell research along with rehabilitation strategies that may have a synergistic outcome when combined together after stroke. Indeed, stem cell transplantation offers a promising new approach and may add to current rehabilitation therapies. By reviewing the pathophysiology of stroke and the mechanisms by which stem cells and rehabilitation attenuate this inflammatory process, we hypothesize that a combined therapy will provide better functional outcomes for patients. Using current preclinical data, we explore the prominent types of stem cells, the existing theories for stem cell repair, rehabilitation treatments inside the brain, rehabilitation modalities outside the brain, and evidence pertaining to the benefits of combined therapy. In this review article, we assess the advantages and disadvantages of using stem cell transplantation with rehabilitation to mitigate the devastating effects of stroke.


2008 ◽  
Vol 24 (3-4) ◽  
pp. E15 ◽  
Author(s):  
Raphael Guzman ◽  
Raymond Choi ◽  
Atul Gera ◽  
Alejandro De Los Angeles ◽  
Robert H. Andres ◽  
...  

✓ The use of stem cell transplantation to restore neurological function after stroke is being recognized as a potential novel therapy. Before stem cell transplantation can become widely applicable, however, questions remain about the optimal site of delivery and timing of transplantation. In particular, there seems to be increasing evidence that intravascular cell delivery after stroke is a viable alternative to intracerebral transplantation. In this review, the authors focus on the intravascular delivery of stem cells for stroke treatment with an emphasis on timing, transendothelial migration and possible mechanisms leading to neuroprotection, angiogenesis, immunomodulation, and neural plasticity. They also review current concepts of in vivo imaging and tracking of stem cells after stroke.


Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3972-3972 ◽  
Author(s):  
Matthias Staudinger ◽  
Christian Kellner ◽  
Matthias Peipp ◽  
Natalie Schub ◽  
Andreas Humpe ◽  
...  

Abstract Although the mortality of autologous stem cell transplantation in contrast to allogeneic is low, in AML patients the lack of immune surveillance as well as contamination of the transplant with residual leukemic stem cells (LSC) limits its use. Therefore, elimination of LSC by targeted therapy may represent a promising therapeutic approach. Recently, CD96 was identified as marker antigen on AML-LSC (Hosen et al., PNAS 104: 11008, 2007). Here, by addressing CD96 with magnetic cell sorting (MACS) or using antibody dependent cellular cytotoxicity (ADCC), new strategies for engineering autologous stem cell grafts or for in vivo targeting of residual AML stem cells are presented. To evaluate the efficacy of depletion of LSC by MACS technology, grafts containing hematopoietic stem cells were spiked with CD96 positive AML cells. Using biotinylated CD96 antibody TH111 raised in our laboratory in combination with anti-biotin-micro beads (Miltenyi Biotech, Bergisch Gladbach, Germany) up to a 1000-fold depletion of targeted cells was achieved. The viability, cell count and the potential of hematopoietic progenitor cells (HPC) to proliferate and differentiate were not affected by this procedure as documented by flow cytometry and colony forming assays. As residual LSC residing within the patient may also account for AML relapse after high-dose chemotherapy and subsequent SCT, eradication of AML stem cells in vivo is desirable. To target CD96+ AML-LSC by ADCC, chimeric antibodies containing wild type or affinity maturated variable regions in combination with an optimized human IgG1Fc were generated by recombinant DNA technologies. Both recombinant antibodies were expressed in Hek 293 cells enriched to homogeneity by affinity chromatography and analyzed for their functional properties. As shown by flow cytometry, the antigen binding affinity of the maturated antibody was enhanced (EC50 0.6 μg/ml vs. 2 μg/ml). Moreover, as analyzed in standard ADCC assays, NK cell mediated lytic properties against CD96-positive target cells were elevated (maximum lysis: 52%) using the affinity maturated chimeric CD96 antibody (EC50: 0.02 μg/ml vs. 0.15 μg/ml). Thus, this CD96 purging strategy avoids unwanted transplantation of AML-LSC and may help to revitalize autologous stem cell transplantation in this indication. Although, specific side effects by CD96 application will have to be considered, this may allow for an additional therapeutic avenue to eliminate in vivo residual AML-LSC in autologous as well as in allogeneic situations. Disclosures: No relevant conflicts of interest to declare.


2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Ping Wang ◽  
Francesco Petrella ◽  
Luca Nicosia ◽  
Massimo Bellomi ◽  
Stefania Rizzo

Stem cell transplantation has been investigated to rescue experimental liver failure and is promising to offer an alternative therapy to liver transplantation for liver diseases treatment. Several clinical studies in this field have been carried out, but the therapeutic benefit of this treatment is still controversial. A major obstacle to developing stem cell therapies in clinic is being able to visualize the cells in vivo. Imaging modalities allow optimization of delivery, detecting cell survival and functionality by in vivo monitoring these transplanted graft cells. Moreover, theranostic imaging is a brand new field that utilizes nanometer-scale materials to glean diagnostic insight for simultaneous treatment, which is very promising to improve stem cell-based therapy for treatment of liver diseases. The aim of this review was to summarize the various imaging tools that have been explored with advanced molecular imaging probes. We also outline some recent progress of preclinical and clinical studies of liver stem cells transplantation. Finally, we discuss theranostic imaging for stem cells transplantation for liver dysfunction and future opportunities afforded by theranostic imaging.


2021 ◽  
Vol 271 ◽  
pp. 03076
Author(s):  
Weibai Chen

Neural stem cells have the ability to proliferation, differentiate and renew, which plays an important role in the growth, maturation and senescence of the human brain. But according to researches, neural stem cells in the brain do not remain active throughout an organism's lifetime. Many neural stem cells become dormant when the brain matures, and may be activated when the body is sick to selectively heal the disease. In recent years, there are many studies on neural stem cells. Joshua[1] and Ting Zhang[2] show that neurodegenerative diseases such as ischemic stroke, Alzheimer's disease and Parkinson's disease can be improved by the transplantation of neural stem cells, however the specific mechanism is not clear. This paper investigates three main questions: Why neural stem cell transplantation is chosen as a treatment? Where does NSCs derive from in clinical transplantation? How does neural stem cell transplantation treat brain diseases? And we also figure out the answers to these three questions. Firstly, transplantation of hypothalamic NSCs can delay the process of aging in the host, and Chemokines and EVs which secreted by neural stem cells can delay aging and defend neurodegenerative diseases. Secondly, the sources of NSCs can be divided into three types. The first is to isolate NSCs from primary tissue and cultivate them in vitro. The second is to produce the required cells by inducing pluripotent stem cells and embryonic stem cells. The third way to get NCS is through transdifferentiation of somatic cells. Thirdly, in brain diseases, transplanted NSCs can migrate from the aggregation site to the site of the disease, reducing damage to the blood-brain barrier, repairing learning and memory abilities that depend on the hippocampus and secreting neurotrophic factors.


2019 ◽  
Vol 2019 ◽  
pp. 1-8
Author(s):  
Manar A. Al Qudah ◽  
Sana’a A. Zarea ◽  
Saoussan A. Kallel-Jallouli

Stem cells as a therapeutic measure for the treatment of different diseases have a great potential to give rise to different mature cells as they could be used to treat HIV-1 patients when provided with the convenient factors. Thus, this paper proposes a new mathematical model, represented by a system of ODEs, to study the effect of stem cell transplantation for HIV-1 patients. Since stem cells lineage passes through many stages to become more specialized cell types, investigating (theorizing) the best stage for these cells to be engrafted was needed. The proposed system of ODEs can help medicine make the right decision about the proposed therapy.


2021 ◽  
Vol 18 (5) ◽  
pp. 6288-6304
Author(s):  
Awatif Jahman Alqarni ◽  
◽  
Azmin Sham Rambely ◽  
Sana Abdulkream Alharbi ◽  
Ishak Hashim ◽  
...  

<abstract><p>Stem cells play a critical role in regulatory operations, overseeing tissue regeneration and tissue homeostasis. In this paper, a mathematical model is proposed and analyzed to study the impact of stem cell transplantation on the dynamical behavior of stroke therapy, which is assumed to be based on transplanting dead brain cells following a stroke. We transform the method of using hierarchical cell systems into a method of using different compartment variables by using ordinary differential equations, each of which elucidates a well-defined differentiation stage along with the effect of mature cells in improving the brain function after a stroke. Stem cells, progenitor cells, and the impacts of the stem cells transplanted on brain cells are among the variables considered. The model is studied analytically and solved numerically using the fourth-order Runge-Kutta method. We analyze the structure of equilibria, the ability of neural stem cells to proliferate and differentiate, and the stability properties of equilibria for stem cell transplantation. The model is considered to be stable after transplantation if the stem cells and progenitor cells differentiate into mature nerve cells in the brain. The results of the model analysis and simulation facilitate the identification of various biologically probable parameter sets that can explain the optimal time for stem cell replacement of damaged brain cells. Associating the classified parameter sets with recent experimental and clinical findings contributes to a better understanding of therapeutic mechanisms that promote the reconstitution of brain cells after an ischemic stroke.</p></abstract>


Neurosurgery ◽  
2017 ◽  
Vol 64 (CN_suppl_1) ◽  
pp. 251-251
Author(s):  
Ayaz M Khawaja ◽  
Maira Mirza ◽  
Gabriel Rodriguez ◽  
Hassan Aziz

Abstract INTRODUCTION There are no neuroprotective and neuroregenerative treatments available for Traumatic Brain Injury (TBI). Clinical trials investigating potential treatments such as therapeutic hypothermia and progesterone have failed. Pre-clinical studies indicate there may be a role of stem-cells in promoting neuroprotection/neuroregeneration in-vivo in animal models of TBI. We aim to provide a pre-clinical literature review into stem-cells as a potential therapeutic option in TBI-animal models. METHODS Using the terms “traumatic brain injury”, “stem-cell”, “preclinical”, and “animal studies”, a literature search was conducted on Pubmed and Google Scholar. Studies were included if there was an in-vivo animal model of TBI with either intravenous or intra-cortical stem-cell transplantation, along-with a control group, and investigated either motor or behavioral outcomes, or a combination. RESULTS >Twenty-seven studies (n = 1184 animals) satisfied the criteria. 774/1184 (65.4%) animals were investigated for outcomes. 17 studies harvested stem-cells from human-source, whereas 10 harvested stem-cells from animal-source. Bone-marrow stromal-cells (BMSC) were used in 17 studies, neural stem-cells (NSC) in 7, and miscellaneous in 3. 450/774 (58.1%) animals received any stem-cell transplantation, whereas 324 were controls. Of animals receiving stem-cell transplantation (450), 339 (75.3%) showed significantly better outcomes relative to control animals in each individual study, with exception of one study. Amongst transplanted animals, functional outcomes did not differ significantly when grouped by stem-cell type (P = 0.553), transplantation route (P = 0.054), and source (P = 0.784). Animals were followed-up until 1 week (n = 5 studies), 2 weeks (n = 10), 4 weeks (n = 5), or >4-weeks (n = 7). CONCLUSION This pre-clinical data demonstrates that stem-cell transplantation may have treatment potential in TBI as shown by improvement in functional outcome in as many as three-quarters of all animals that were treated with stem-cells. This data provides a foundation for the design of clinical translational studies.


2019 ◽  
Vol 14 (7) ◽  
pp. 703-714 ◽  
Author(s):  
Aimaiti Yasen ◽  
Tuerhongjiang Tuxun ◽  
Shadike Apaer ◽  
Wending Li ◽  
Yusufukadier Maimaitinijiati ◽  
...  

Stem cell transplantation exhibited a promising lifesaving therapy for various end-stage liver diseases and could serve as a salvaging bridge until curative methods can be performed. In past decades, mature hepatocytes, liver progenitor cells, mesenchymal stem cells and induced pluripotent stem cells have been practiced in above settings. However, long-term survival rates and continuous proliferation ability of these cells in vivo are unsatisfactory, whereas, fetal liver stem cells (FLSCs), given their unique superiority, may be the best candidate for stem cell transplantation technique. Recent studies have revealed that FLSCs could be used as an attractive genetic therapy or regenerative treatments for inherited metabolic or other hepatic disorders. In this study, we reviewed current status and advancements of FLSCs-based treatment.


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