Victoria A Stark, Caroline O B Facey, Lynn M Opdenaker, Jeremy Z Fields, Bruce M Boman
{"title":"Differential miRNA Expression Contributes to Emergence of Multiple Cancer Stem Cell Subpopulations in Human Colorectal Cancer.","authors":"Victoria A Stark, Caroline O B Facey, Lynn M Opdenaker, Jeremy Z Fields, Bruce M Boman","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>One reason for lack of efficacy in cancer therapeutics is tumor heterogeneity. We hypothesize that tumor heterogeneity arises due to emergence of multiple Cancer Stem Cell (CSC) subpopulations because miRNAs regulate expression of stem cell genes in CSCs. Our goal was to determine if: i) multiple CSC subpopulations exist in a human CRC cell population, and ii) miRNAs are differentially expressed in the different CSC subpopulations. We discovered that at least four different CSC populations (ALDH1, CD166, LGR5, and LRIG1) exist in the HT29 cell line. CSC subpopulations were quantified using co-staining for multiple stem cell markers, isolated using FACS, and analyzed by NanoString miRNA profiling. The miRNA expression pattern in each CSC subpopulation was analyzed relative to miRNA expression patterns in other CSC subpopulations. Messenger RNAs predicted to be targeted by the up-regulated miRNAs in each CSC subpopulation were: 1) identified using bioinformatics analyses, and 2) classified according to their predicted functions using David functional annotation analyses. We found multiple CSC subpopulations with a unique miRNA signature in each CSC subpopulation. Notably, the miRNAs expressed within one CSC subpopulation are predicted to target and down-regulate the CSC genes and pathways that establish the other CSC subpopulations. Moreover, mRNAs predicted to be targeted by miRNAs in the different CSC subpopulations have different cellular functional classifications. That different CSC subpopulations express miRNAs that are predicted to target CSC genes expressed in other CSC subpopulations provides a mechanism that might explain the co-existence of multiple CSC subpopulations, tumor heterogeneity, and cancer therapy resistance.</p>","PeriodicalId":89694,"journal":{"name":"Journal of stem cell research & therapy","volume":"13 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10972542/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140308228","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Marco-Brualla Joaquín, Gallego-Lleyda Ana, Sanz Moreno Jara, De Paula, Fernández Vicente Pablo, Martínez-Lostao Luis, Lapuente Fernández Juan Pedro, Anel Bernal Luis Alberto
{"title":"Endogenous Soluble TRAIL Contributes to the Survival and Growth of Human Mesenchymal Stem Cells","authors":"Marco-Brualla Joaquín, Gallego-Lleyda Ana, Sanz Moreno Jara, De Paula, Fernández Vicente Pablo, Martínez-Lostao Luis, Lapuente Fernández Juan Pedro, Anel Bernal Luis Alberto","doi":"10.23937/2469-570X/1410072","DOIUrl":"https://doi.org/10.23937/2469-570X/1410072","url":null,"abstract":"Background: TNF-related apoptosis-inducing ligand (TRAIL) is known to induce caspase-dependent apoptosis in tumor cells, while sparing normal cells. However, TRAIL is also able to induce proliferation in cells that are resistant to cell death induction, since it can also activate NF-κB-dependent signaling pathways. Human mesenchymal stem cells (hMSC) transfected with TRAIL have been used to treat cancer, with promising results in pre-clinical models, especially in gliomas. Regarding endogenous TRAIL expression in hMSC or its possible role in cell death, proliferation or differentiation, not much has been explored as yet. Methods: Cell death induction by soluble TRAIL (sTRAIL) or by TRAIL associated with liposomes (LUV-TRAIL) on hMSC was studied by annexin-V-FITC and 7-AAD staining and flow cytometry. The effect of sTRAIL, LUV-TRAIL or a blocking anti-TRAIL mAb on cell growth was studied by uptake of 5-bromo-2’-deoxyuridine (BrdU). Cell morphology after the treatments was studied by phase microscopy. Exosomes were separated from cell supernatant by sequential centrifugations and ultracentrifugation. Endogenous TRAIL expression in hMSC or in their derived exosomes was studied by immunoblot and flow cytometry. Results: We demonstrated that exogenous TRAIL alone, either in soluble form or associated with liposomes (LUVTRAIL), does not affect growth of hMSC. In addition, it is also unable to induce cell death in these cells. Nevertheless, endogenous TRAIL from hMSC did affect positively their proliferation in combination with growth factors present in the serum. We demonstrated the expression of endogenous TRAIL in hMSC, mainly with an intracellular distribution, and showed that it is secreted to the culture supernatant in soluble form, but not in association with exosomes, contributing in this way to hMSC viability and growth. Conclusion: These observations could be important if hMSC transfected with TRAIL are used as tumor treatment or in regenerative medicine, since secreted TRAIL could exert its anti-tumoral effect at the same time as hMSC would persist.","PeriodicalId":89694,"journal":{"name":"Journal of stem cell research & therapy","volume":"8 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44988398","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Embryonic Development And Adult Homeostasis","authors":"N. Itoh","doi":"10.35248/2157-7633.21.11.E495","DOIUrl":"https://doi.org/10.35248/2157-7633.21.11.E495","url":null,"abstract":"","PeriodicalId":89694,"journal":{"name":"Journal of stem cell research & therapy","volume":"11 1","pages":"1-1"},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"69974934","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Loss of Tissue Regenerative Capacity in Aging - The Tendon","authors":"Sandra Carvalho, Valério Margarida Pimenta Queiroz, Ferro Inês Monteiro, Campos Inês, C. Lina","doi":"10.23937/2469-570x/1410071","DOIUrl":"https://doi.org/10.23937/2469-570x/1410071","url":null,"abstract":"Intrinsic to the process of aging is the loss of the ability to regenerate of different organs and tissues, becoming more susceptible to aggression and impaired function. Tendon aging is a complicated process following, however, similar mechanisms of other tissues proposed model of the “Hallmarks of Aging”, by López-Otín, et al [1]. Tendon structure and cellular composition is also unique, which makes scientific research in this field both a very specific and select task. Mesenchymal Stem Cells (MSCs), more specifically, Tendon stem/progenitor cells (TSPCs) may be of key importance. Tendon disease is one of the most common entities worldwide, and is currently increasing with the augment of the human life-expectancy. This review proposes to make a short summary of the state of the art in both the aging tendon and its available treatment target potentials.","PeriodicalId":89694,"journal":{"name":"Journal of stem cell research & therapy","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45698167","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Broekhoven Amber van, Woudstra Linde, Meinster Elisa, Haren Laura van, Kay Amber M, Koopman Marit, Morrison Martine C, Helder Marco N, Juffermans Lynda J, Schalkwijk Casper G, Niessen Hans WM, Vonk Alexander BA, Krijnen Paul AJ
{"title":"Stembell Therapy Reduces Macrophages in Atherosclerotic Aortic Valves after Myocardial Infarction","authors":"Broekhoven Amber van, Woudstra Linde, Meinster Elisa, Haren Laura van, Kay Amber M, Koopman Marit, Morrison Martine C, Helder Marco N, Juffermans Lynda J, Schalkwijk Casper G, Niessen Hans WM, Vonk Alexander BA, Krijnen Paul AJ","doi":"10.23937/2469-570x/1410069","DOIUrl":"https://doi.org/10.23937/2469-570x/1410069","url":null,"abstract":"Background: Previously, we have shown that StemBell therapy (i.e. mesenchymal stem cell-microbubble complexes subjected to ultrasound) reduced plaque inflammation and plaque destabilization in the aortic root, and thereby inhibited atherosclerosis exacerbation after myocardial infarction (MI). MI also has an effect on heart valves as it increases valve thickness and remodeling. Moreover, hemodynamic disturbances following MI have also been suggested to affect aortic valve (AV) pathology. Therefore, we have analyzed StemBell therapy on AV after MI. Methods: In atherosclerotic Apolipoprotein E-deficient mice that were fed a high-fat Western diet, MI was induced via permanent left coronary artery ligation. Six days postMI, the mice received either 5 × 105/100 μL StemBells or vehicle intravenously. The effects of StemBell treatment on the AV were determined 28 days post-MI via (immuno)histochemical analyses. Results: In all mice, we observed morphological signs of AV sclerosis including thickened valve leaflets, acellularity, glycosaminoglycan (GAG) transformation and fibrosis, but without evidence of mineralization, suggestive for more early-stage AV disease in our mouse model. StemBell therapy resulted in a significantly decreased infiltration of Mac3+ macrophages in the AV, without significantly affecting CD163+ macrophages, CD45+ leukocytes and monocytic chemoattractants. The advanced glycation end products (AGEs) Nε-(carboxymethyl) lysine (CML) and methylglyoxal (MGO) were decreased in the AV of StemBell-treated mice, albeit not significantly. No significant effects were observed in AV thickness, fibrosis, GAGs, lipidand calcium-deposits. StemBell therapy did however increase AV iron deposits, although not significant. Conclusion: StemBell therapy reduced macrophage infiltration of AV after MI without changing valve morphology.","PeriodicalId":89694,"journal":{"name":"Journal of stem cell research & therapy","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43648312","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Liang Qiu-yun, C. Juan, L. Yong-heng, Wei-Zhang, Xiao En-hua
{"title":"Sodium Butyrate Pre-Treatment Enhances Hepatic Differentiation of Bone Marrow Mesenchymal Stem Cells Under Liver-Specific Factors Induction In Vitro","authors":"Liang Qiu-yun, C. Juan, L. Yong-heng, Wei-Zhang, Xiao En-hua","doi":"10.23937/2469-570x/1410068","DOIUrl":"https://doi.org/10.23937/2469-570x/1410068","url":null,"abstract":"Aims: It is crucial to establish an effective method to improve mesenchymal stem cells (MSCs) hepatic differentiation in mesenchymal stem cells transplantation. Herein, we aim to explore whether sodium butyrate (NaB) enhances hepatic differentiation of bone marrow mesenchymal stem cells (BM-MSCs) under liver-specific factors induction in vitro. Methods: We isolated BM-MSCs from the mononuclear cell fraction of rabbit bone marrow samples, and identified these cells by immunophenotype analysis. We then investigated the effects of different concentrations and different induced conditions. The histone deacetylase inhibitor NaB induced hepatic differentiation of BM-MSCs under liver-specific factors induction in vitro. BM-MSCs cultured in basic medium without the differentiation stimuli were set as the control. Morphological features, liver-specific gene and protein expression, and functional analyses were assessed to evaluate hepatic differentiation of BM-MSCs. Results: Our results showed that the persistence of NaB inhibited the expression of liver-specific protein expression in a dose-dependent manner. When NaB was continuously induced, all the four concentrations used were not conducive to induce hepatocyte transformation, but the low concentrations (0.5 and 1.0 mM) were relatively better. We found that the induction efficiency of NaB 24h pre-treatment was higher than that of NaB continuous intervention for 0.5 mM or 1.0 mM conditions, and higher than liver-specific factors such as hepatocyte growth factor (AGF) and epidermal growth factor (EGF) without NaB. Conclusion: Continuous NaB treatment can inhibit BMMSCs proliferation with concentration-dependence in a certain concentration range. 24h pre-treatment can enhance hepatic differentiation of BM-MSCs under liver-specific factors induction in vitro.","PeriodicalId":89694,"journal":{"name":"Journal of stem cell research & therapy","volume":"7 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43507745","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Biplabendu Talukdar, Swarnendu Datta, Priyodarshi Sengupta, P. Mukherjee, Ushnish Chakravarty
{"title":"Contamination Rates by Delivery Method of Human Umbilical Cord Blood Samples in the United Arab Emirates and Gulf Cooperation Council Countries","authors":"Biplabendu Talukdar, Swarnendu Datta, Priyodarshi Sengupta, P. Mukherjee, Ushnish Chakravarty","doi":"10.35248/2157-7633/20.10.458","DOIUrl":"https://doi.org/10.35248/2157-7633/20.10.458","url":null,"abstract":"Coronary heart disease (CAD) is the most common cause of death and disability in developed and developing countries. Globally, 17.5 million deaths were recorded in 2012 due to this disease. Over 75% of deaths, observed in developing countries. Mortality from cardiovascular disease is declining rapidly in developed countries. While deaths or disabilities from myocardial diseases have increased in developing countries due to industrialization, urbanization, changes in dietary habits and changes in people's lifestyles. Percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CAP) is the gold standard treatment for patients with ischemic heart disease. Organ and tissue transplants can modify the disease, but the availability of donor tissue, tissue matching and organ harvesting are important parameters for a successful transplant. Recently, the human umbilical cord (HUC) has been studied extensively and current studies have revealed that the HUC can be the potential substitute for vessels, ligaments, tendons, and bones. Human cord lining epithelial cells (CLEC) do not express MHC class II HLA-DR antigen, while unclassical MHC class Ib antigen HLA-G and HLA-E has some immunomodulatory roles . The HLA-G protein decreases the production of CD8 and natural killer cells. Therefore, the human umbilical cord can be used as a substitute for artery or venous graft in vascular and reconstructive surgery. We hypothesize that human umbilical cord vessels (HUC) may be an effective new substitute for coronary artery reconstruction for those with coronary artery disease as well as peripheral vascular disease. Our hypothesis can be summarized as follows: 1. Allogenic substitute: human umbilical cord, as a natural tissue product for the reconstruction of the diseased coronary artery. It is collected from the mother of the newborn who has been screened for transmission transmitted disease (TTD) immediately after parturition in a sterile manner. Umbilical arteries / veins help in the surgical reconstruction of damaged vessels in another person. HUC containing two arteries and a vein. It is also established that the HUC is a source of goods for Mesenchymal stem cells (HUC-MSC) which can be differentiated into several lineage-specific cells which form bone, cartilage, liver, heart tissue, etc. In addition, it is also established that Wharton's jelly which surrounds the human umbilical vein (HUV) is rich in growth factors. Thus, HUC, with such a composition of MSC, living cells and growth factors, could be a promising material for the restoration of the function of the coronary artery 2. Autologous surrogate: The umbilical cord of an individual, banked right after birth, can come in handy for future use. It could be directly applied to directly reconstruct the patient's own coronary artery. We hypothesize that the autologous HUC can also be used to reconstruct the coronary artery. Autologous HUC offers the following advantages: First, HUC-MSCs could di","PeriodicalId":89694,"journal":{"name":"Journal of stem cell research & therapy","volume":"10 1","pages":"1-1"},"PeriodicalIF":0.0,"publicationDate":"2020-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43042777","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The Blood Levels of the Amino Acid Kynurenine and Indoloxigenase are Predictive of Acute Graft Versus Host Disease (aGVHD)","authors":"D. Ferreira, I. Silva, EG Lo Turco, Jsr Oliveira","doi":"10.23937/2469-570x/1410065","DOIUrl":"https://doi.org/10.23937/2469-570x/1410065","url":null,"abstract":"The main barrier to the success of hematopoietic stem cell transplantation (HSCT) is acute graft versus host disease (aGVHD). The risk factors for aGVHD are mainly clinical and can be improved if additional biological factors are incorporated, such as the metabolomic profile. It is known that the levels of various metabolites measured are important in the process of immunoregulation [1]. In our population study we investigated the systemic metabolic profile for 26 (Group I) allotransplant recipients. The metabolomics study was carried out by Targeted Mass Spectrometry. Plasma samples of the 26 patients were collected before the Conditioning Regimen of HSCT. All patients were clinically evaluated until 2 years after transplant and then Group I was subdivided into subgroup IA: 16 patients that presented aGVHD and subgroup IB: 10 patients without aGVHD. When comparing the metabolites dosages from subgroup IA with those of subgroup IB, it was observed that 25 metabolites We then verified by bioinformatics analyses that the ratio Kynurenine/Tryptophan which estimates the Indoloxigenase (IDO) enzyme activity. Kynurenine and the IDO enzyme are metabolites that present clinical evidence in the literature regarding the immunotolerance process. The role of IDO enzyme in the maintenance of the allogeneic fetus in pregnant women was verified in an animal model in 1998 by Mellor and Munn. Thus, the pre-transplant analysis of the metabolomics profile of allotransplant recipients seems to contribute to a better understanding of immunological process and lower dosages of Kynurenine and IDO activity enzyme pre-transplant can identify patients at higher risk for developing aGVHD. RESEaRCh aRTICLE","PeriodicalId":89694,"journal":{"name":"Journal of stem cell research & therapy","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46202378","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
B. Bhogal, D. Royal, R. Boer, J. Phillips, A. Knight
{"title":"Live Fetal Stem Cells Therapy, Anti-Neu5Gc Responses and Impact on Human Heart, Brain and Immune System","authors":"B. Bhogal, D. Royal, R. Boer, J. Phillips, A. Knight","doi":"10.35248/2157-7633/20.10.459","DOIUrl":"https://doi.org/10.35248/2157-7633/20.10.459","url":null,"abstract":"Fetal stem cells used for clinical applications in humans can cause xenogenic immune reactions and impact vital organs by immune dysregulation. Animal stem/fetal cells express glycan antigens, such as Neu5Gc. Humans do not produce these antigens. Two major sialic acids are described in mammalian cells, Neu5Gc, the N-glycolylneuraminic acid, and Neu5Ac the N-acetylneuraminic acid. Neu5Gc synthesis starts from the N-acetylneuraminic acid (Neu5Ac) precursor modified by a hydroxylic group addition catalyzed by cytidinemonophospho-N-acetyl-neuraminic acid hydroxylase-Neu5Ac hydroxylase enzyme (CMAH). CMAH was inactivated by a 92 base pairs deletion over 2 million years ago and is non-functional in humans, Neu5Gc as well as the peptides derived from fetal cells is remarkably immunogenic for humans and promotes inflammation, arthritis, cancer. Accumulating evidence shows that xenotransplantation of animal stem cells results in inflammation autoimmune responses and immune-rejection and may cause death. Here we highlight the serious deleterious effects of the presence of Neu5Gc antigen in animal fetal cells and the effects of presence and absence of Neu5Gc antibodies in humans acquired through the consumption of animal products. There are many reports of immune reactions to animal stem cells and their derivatives. Insect biterelated anti-alpha-gal and anti-Neu5Gc antibodies, and those induced by animal cells, cause “immune enhancement” and serious allergic reactions and or immune-pathology leading to irreversible damage to vital organs in the human body. Therefore needless to say that the use of animal stem cells and their derivatives being marketed as nutritional supplements are harmful for human use and should not be used either as oral supplements or as peptide injections. There is no evidence of their safety or efficacy for treating disease conditions or for their anti-aging effects. Neu5Gc (xeno-antigen), are produced by Animal Stem/fetal Cells and the peptides derived from them. Remarkably, Neu5Gc is a xeno-antigen for humans, and promote inflammation, arthritis, cancer, and xeno-transplantation of animal stem cells can result in inflammation autoimmune responses and immune-rejection (GVHD) and death.","PeriodicalId":89694,"journal":{"name":"Journal of stem cell research & therapy","volume":"10 1","pages":"1-8"},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"69975414","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
P. Everts, J. Ferrell, C. B. Mahoney, G. Flanagan, M. Roman, Rowan V. Paul, Natalie Stephens, K. Mautner
{"title":"A Comparative Quantification in Cellularity of Bone Marrow Aspirated with two New Harvesting Devices, and The Non-equivalent Difference Between A Centrifugated Bone Marrow Concentrate And A Bone Marrow Aspirate As Biological Injectates, Using A Bi-Lateral Patient Model","authors":"P. Everts, J. Ferrell, C. B. Mahoney, G. Flanagan, M. Roman, Rowan V. Paul, Natalie Stephens, K. Mautner","doi":"10.35248/2157-7633/20.10.461","DOIUrl":"https://doi.org/10.35248/2157-7633/20.10.461","url":null,"abstract":"The first aim of this study was to examine the cellularity and quality of autologous bone marrow aspirates harvested with two novel FDA-cleared devices, namely the Aspire™ bone marrow aspiration system (AS-BMAS) and the Marrow Cellution bone marrow aspiration device (MC-BMAD). Compared to traditional bone marrow harvesting needle systems, both these devices have a closed distal tip, avoiding preferential marrow collection (peripheral blood aspiration) from deeper cavity regions, whereas the side holes facilitate more horizontal marrow extraction. In all patients, a similar harvesting technique was used. The second aim was to demonstrate the effectiveness of mechanical centrifugation of a large volume of extracted bone marrow to produce a bone marrow concentrate (BMC). Finally, we directly compared bone marrow constituents aspirated with MC-BMAD with a BMC, generated by centrifugation of bone marrow harvested using the AS-BMAS. A bi-lateral patient model was used for all comparisons. All cellular analyses included the measurement of Colony-Forming Units-fibroblasts (CFU/f) levels, CD34+cells/ml, Total Nucleated Cells (TNCs)/ml, platelets/ml, and Red Blood Cells (RBCs)/ml in a single, FDA-approved laboratory, compliant with Good Manufacturing Practice regulations. A total of 12 patients consented to the study. In the direct BMA comparison, the AS-BMAS bone marrow yielded significantly higher CFU/f counts and TNC concentrations than the MC-BMAD (1,060/ml, 33.5 × 106/ml, and 610/ml and 28.6 × 106/ml, respectively), with comparable platelet and RBC concentrations. Data following BMA concentration to produce a BMC revealed highly significant cell yields, fewer RBCs, and lower hematocrit (HCT). A direct cellular comparison between the aspirate of the MCBMAD and centrifugated BMC following AS-BMAS marrow extraction showed highly significant differences in cellularity. The AS-BMAS produced cell concentrations of CFU/f, CD34+ cells, TNCs, platelets, and RBCs that were comparable, or greater than, the predicate device. We believe that concentrating bone marrow is a consistent and safe method to produce a BMC that has the potential to be clinically effective. Furthermore, data indicate a non-equivalent difference in BMC cellularity, when compared to a non-filtered and non-centrifugated BMA for clinical use.","PeriodicalId":89694,"journal":{"name":"Journal of stem cell research & therapy","volume":"10 1","pages":"1-10"},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"69975547","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}