scholarly journals 193 Does Stem Cell Therapy Hold Promise In The Management Of Traumatic Brain Injuries? A Literature Review of Animal Studies

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.

2021 ◽  
Vol 22 (9) ◽  
pp. 4357
Author(s):  
Sahng G. Kim

Despite the recent explosion of investigations on dental pulp regeneration using various tissue engineering strategies, the translation of the findings from such studies into therapeutic applications has not been properly achieved. The purpose of this scoping review was to systematically review the efficacy of mesenchymal stem cell transplantation for dental pulp regeneration. A literature search was conducted using five electronic databases from their inception to January 2021 and supplemented by hand searches. A total of 17 studies, including two clinical trials and 15 animal studies using orthotopic pulp regeneration models, were included for the review. The risk of bias for the individual studies was assessed. This scoping review demonstrated that the regeneration of vascularized pulp-like tissue was achieved using the stem cell transplantation strategy in animal models. Autologous cell transplantation in two clinical studies also successfully regenerated vascularized vital tissue. Dental pulp stem cell subpopulations, such as mobilized dental pulp stem cells, injectable scaffolds such as atelocollagen, and a granulocyte-colony forming factor, were the most commonly used for pulp regeneration. The overall risk of bias was unclear for animal studies and was moderate or judged to raise some concerns for clinical studies. More high-quality clinical studies are needed to further determine the safety and efficacy of the stem cell transplantation strategy for dental pulp regeneration.


Neurotrauma ◽  
2018 ◽  
pp. 373-386
Author(s):  
Dong Sun

Traumatic brain injury (TBI) is a global public health concern, with limited treatment options available. Despite improving survival rates after TBI, there is no effective treatment to improve the neural structural repair and functional recovery of patients. Neural regeneration through neural stem cells, either by stimulating endogenous neural stem cells or by stem cell transplantation, has gained increasing attention as a potential strategy to repair and regenerate the injured brain. This chapter summarizes strategies that have been explored to enhance endogenous neural stem cells-mediated regeneration and recent developments in cell transplantation studies for post-TBI brain repair with varying types of cell sources.


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.


2005 ◽  
Vol 15 (2) ◽  
pp. 143-148 ◽  
Author(s):  
Luca Longhi ◽  
Elisa R. Zanier ◽  
Nicolas Royo ◽  
Nino Stocchetti ◽  
Tracy K. McIntosh

2019 ◽  
Vol 25 (10) ◽  
pp. 1099-1104 ◽  
Author(s):  
Ding Zhao ◽  
Yijun Liu ◽  
Chi Ma ◽  
Guishan Gu ◽  
Dong-Feng Han

Osteonecrosis of the femoral head (ONFH) is a common disease that occurs frequently. Due to various etiologies, the blood supply directed to the femoral head is interrupted in patients with ONFH. This disease can result in degeneration and necrosis of the subchondral bone of the femoral head, which ultimately cause a collapse of the femoral head. Of note, ONFH can extremely affect the quality of living of patients with a high disability rate. Also, this disease often includes middle-aged and younger people. However, effective treatments of ONFH are still challenging in clinics. In recent years, stem cells have been profoundly studied and a relevant new technology has been developed rapidly and applied for regenerative medicine. A number of reports have demonstrated successful results of the treatment of ONFH by using stem cell transplantation. By the combination of minimally invasive hip decompression and injection of mesenchymal stem cells into the necrotic lesion, the retrospective analysis of patients treated revealed that significant pain relief was observed in 86% patients and they had no major complications after treatment. Thus, stem cell transplantation is anticipated to be applied as an innovative approach in the treatment of ONFH. This review will summarize results obtained from recent human and animal studies, which include the pathophysiological process of ONFH, current techniques and effects of using stem cells on the treatment of ONFH together with pharmacological aspects. Overall, the current evidence reveals the treatment of ONFH using stem cell technology as promising. Nonetheless, additional in-depth studies are necessary to better explore the application of this technology and seek more ideal approaches to minimize difficulties related to stem cells.


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