scholarly journals Bone Marrow Stem Cell Derived Paracrine Factors for Regenerative Medicine: Current Perspectives and Therapeutic Potential

2011 ◽  
Vol 2011 ◽  
pp. 1-14 ◽  
Author(s):  
Tom J. Burdon ◽  
Arghya Paul ◽  
Nicolas Noiseux ◽  
Satya Prakash ◽  
Dominique Shum-Tim
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Cell Therapy ◽  
Therapeutic Potential ◽  
Paracrine Factors ◽  
Beneficial Effects ◽  
Cytokines And Chemokines ◽  
Survival Pathways ◽  
Wide Range ◽  
Technical Issues

During the past several years, there has been intense research in the field of bone marrow-derived stem cell (BMSC) therapy to facilitate its translation into clinical setting. Although a lot has been accomplished, plenty of challenges lie ahead. Furthermore, there is a growing body of evidence showing that administration of BMSC-derived conditioned media (BMSC-CM) can recapitulate the beneficial effects observed after stem cell therapy. BMSCs produce a wide range of cytokines and chemokines that have, until now, shown extensive therapeutic potential. These paracrine mechanisms could be as diverse as stimulating receptor-mediated survival pathways, inducing stem cell homing and differentiation or regulating the anti-inflammatory effects in wounded areas. The current review reflects the rapid shift of interest from BMSC to BMSC-CM to alleviate many logistical and technical issues regarding cell therapy and evaluates its future potential as an effective regenerative therapy.

Initial Mechanistic Screening of Transamniotic Stem Cell Therapy in the Rodent Model of Spina Bifida: Host Bone Marrow and Paracrine Activity

2020 ◽  
Vol 47 (12) ◽  
pp. 902-911
Author(s):  
Stefanie P. Lazow ◽  
Sarah A. Tracy ◽  
Alexander V. Chalphin ◽  
Ina Kycia ◽  
David Zurakowski ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Growth Factor ◽  
Spina Bifida ◽  
Cell Therapy ◽  
Stem Cell Therapy ◽  
Transforming Growth Factor ◽  
Cell Activity ◽  
Paracrine Factors ◽  
Fetal Bone

<b><i>Purpose:</i></b> Transamniotic stem cell therapy (TRASCET) with mesenchymal stem cells (MSCs) can induce spina bifida coverage with neoskin. We initiated a mechanistic analysis of this host response. <b><i>Methods:</i></b> Pregnant dams (<i>n</i> = 28) exposed to retinoic acid to induce fetal spina bifida were divided into an untreated group and 2 groups receiving intra-amniotic injections on gestational day 17 (E17; term = E21–22) of either amniotic fluid-derived MSCs (afMSCs; <i>n</i> = 105) or saline (<i>n</i> = 107). Gene expressions of multiple paracrine and cell clonality markers were quantified at term by RT-qPCR at the defect and fetal bone marrow. Defects were examined histologically for neoskin coverage. Comparisons were by Mann-Whitney U tests and logistic regression. <b><i>Results:</i></b> Defect coverage was associated with significant downregulation of both epidermal growth factor (<i>Egf</i>; <i>p</i> = 0.031) and fibroblast growth factor-2 (<i>Fgf-2</i>; <i>p</i> = 0.042) expressions at the defect and with significant downregulation of transforming growth factor-beta-1 (<i>Tgfb-</i>1<i>; p</i> = 0.021) and <i>CD45</i> (<i>p</i> = 0.028) expressions at the fetal bone marrow. <b><i>Conclusions:</i></b> Coverage of experimental spina bifida is associated with local and bone marrow negative feedback of select paracrine factors, as well as increased relative mesenchymal stem cell activity in the bone marrow. Further analyses informed by these findings may lead to strategies of nonsurgical induction of prenatal coverage of spina bifida.

A pilot study with autologous bone marrow-derived stem cell therapy in patients with severe peripheral arterial disorder

2008 ◽  
Vol 149 (12) ◽  
pp. 531-540 ◽  
Author(s):  
Zoltán Boda ◽  
Miklós Udvardy ◽  
Katalin Farkas ◽  
Judit Tóth ◽  
László Jámbor ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Pilot Study ◽  
Cell Therapy ◽  
Color Doppler ◽  
Autologous Bone Marrow ◽  
Thromboangiitis Obliterans ◽  
Arteriosclerosis Obliterans ◽  
Autologous Bone ◽  
Peripheral Arterial

Súlyos perifériás artériás érbetegségekben a gyógyszeres és/vagy érsebészeti beavatkozások kimerülését követően a tűrhetetlen fájdalom, kiterjedt végtagi fekélyek, gangraenák megszüntetésének egyetlen módja a végtag amputációja. Betegek és módszerek: A szerzők – hazánkban elsőként – 5 előrehaladott perifériás artériás érbetegben (1 arteriosclerosis obliterans és 4 thromboangiitis obliterans) autológ csontvelői eredetű őssejtterápiát végeztek. A csontvelői őssejteket (CD34+ sejtek) crista biopsia végzésével nyerték. Mágneses sejtszeparálással CD34+ sejtszuszpenziót állítottak elő. Meghatározták a CD34+, CD133+ és CD45± sejtek számát és arányát. Az őssejtszuszpenziót intramuscularis injekció formájában a beteg végtagba juttatták vissza. Betegenként 0,37–1,14 × 10 5 /kg őssejt visszaadására került sor. Betegeiket 12 hónapig követték. Vizsgálatok történtek a beavatkozás előtt és után (1, 3, 6, 9 és 12 hónappal). Klinikai vizsgálatok: nyugalmi fájdalom, dysbasiás távolság, ischaemiás fekélyek gyógyhajlama, boka-kar index. Laboratóriumi vizsgálatok: angiográfia (az őssejtterápia előtt és után 1 és 6 hónappal), duplex ultrahang- és lézer-Doppler-scan, transcutan oxigéntenzió mérése, az endothelfunkciók vizsgálata. Eredmények: A nyugalmi fájdalom mind az öt betegük esetében megszűnt. A dysbasiás távolság szignifikánsan nőtt (36/440 m). Három beteg végtagi ischaemiás fekélye begyógyult, egy beteg nagyméretű fekélye lényegesen kisebbé és felületesebbé vált, egy betegben a végtagi fekély nem változott. A kezelt oldalon a boka-kar index szignifikánsan nőtt (0,41/0,83) tizenkét hónappal az őssejtterápiát követően, s nem változott az ellenoldalon. Három betegben tapasztaltak számottevő változást angiográfiával az őssejtterápia után hat hónappal. Csak szerény javulást észleltek color-Doppler- és lézer-Doppler-vizsgálatokkal. Az őssejtterápia előtt és után 1, 6 és 12 hónappal a transcutan oxigéntenzió-értékek a lábháton 18,10/16,78/23,83/37,50 Hgmm-re, míg a lábszáron 36,66/31,25/45,00/37,30 Hgmm-re változtak. A makro- és mikrocirkulációs paraméterek nem mutattak javulást az őssejtterápiát követően 1 hónappal, azonban az őssejtterápia után 3, 6, 9 és 12 hónappal már mérhető javulást tapasztaltak. Szövődményt, mellékhatást nem észleltek. Következtetések: Klinikai eredményeik alapján az autológ csontvelői eredetű őssejtterápiát hatásosnak, tartósnak és biztonságosnak tartják előrehaladott perifériás artériás érbetegségben. Szükség van további klinikai tapasztalatgyűjtésre.

Abstract 295: The Stem Cell Therapy to Prevent Expansion of Abdominal Aortic Aneurysm (STOP-AAA) Trial: Rationale and Design

2014 ◽  
Vol 34 (suppl_1) ◽  
Author(s):  
Michael P Murphy ◽  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Abdominal Aortic Aneurysm ◽  
Aortic Aneurysm ◽  
Cell Therapy ◽  
Autologous Bone Marrow ◽  
Research Network ◽  
Stem Cell Population ◽  
Abdominal Aortic ◽  
Autologous Bone

Background: Abdominal aortic aneurysm (AAA) is the 13 th leading cause of death in the United States. The only options for treatment at present for AAA are open surgical and endovascular repair, both of which are associated with significant morbidity, mortality, and expense.Thus AAA represents an unmet medical need. AAA pathogenesis is a multifactorial inflammatory process characterized by activation of T-cells,macrophages and neutrophils resulting in degradation of the aortic wall. Mesenchymal stromal cells (MSCs) suppress T-cell and macrophage activation, inhibit matrix metalloproteinases and have been shown to decrease aneurysm expansion in murine models. Methods: The STOP-AAA trial, from the NHLBI funded Cardiovascular Cell Therapy Research Network, is a randomized, double-blind, placebo-controlled trial evaluating the safety and efficacy of autologous bone marrow derived MSCs in suppressing expansion of small AAA (35-50mm).Forty patients will be randomized in a 1:1 fashion to receive systemic administration of placebo or 3 doses of 2x10 6 MSC/kg. at baseline, 24, and 52 weeks. The primary endpoint will be change in AAA diameter at 18 months as measured by a single blinded observer using contrast enhanced helical computed tomographic angiography (CTA).The secondary endpoints include time to elective repair, incidence of AAA related deaths and rupture,change in aortic mural inflammation at 18 months as quantified by F18-fluorodeoxyglucose (FDG) uptake with integrated positron emission tomography and computed tomography (PET/CT), changes in circulating mRNA, microRNA, and inflammatory cell profiles, changes in serum cytokine levels, and major adverse cardiac events. Conclusion: The STOP-AAA will be the first in man study to assess the efficacy of autologous bone marrow derived MSCs to suppress AAA expansion. Furthermore the data collected from this novel trial will provide unique mechanistic insights in the immunomodulatory properties of this stem cell population.

scholarly journals Cell rounding causes genomic instability by dissociation of single-stranded DNA-binding proteins

2018 ◽  
Author(s):  
Qian Guo ◽  
Xianglu Liao ◽  
Xingwu Wang ◽  
Ling Liu ◽  
Bao Song
Keyword(s):  
Stem Cell ◽  
Dna Binding ◽  
Cell Therapy ◽  
Genomic Instability ◽  
Stem Cell Therapy ◽  
Binding Proteins ◽  
Dna Binding Proteins ◽  
Single Stranded Dna ◽  
Cell Rounding ◽  
Wide Range

AbstractGenomic instability can cause a wide range of diseases, including cancer and cellular senescence, which is also a major challenge in stem cell therapy. However, how a single event can cause extremely high levels of genomic instability remains unclear. Using our developed method, cell in situ electrophoresis (CISE), and models of normal, cancer, and embryonic stem cells, we found that cell rounding as a catastrophic source event ubiquitously observed in vivo and in vitro might lead to large-scale DNA deprotection, genomic instability, chromosomal shattering, cell heterogeneity, and senescent crisis by dissociation of single-stranded DNA-binding proteins (SSBs). Understanding the mechanism may facilitate the development of clinical strategies for cancer therapy, improve the safety of stem cell therapy, and prevent pathological aging.

Autologous bone marrow-derived stem cell therapy in heart disease: Discrepancies and contradictions

2013 ◽  
Vol 168 (4) ◽  
pp. 3381-3403 ◽  
Author(s):  
Darrel P. Francis ◽  
Michael Mielewczik ◽  
David Zargaran ◽  
Graham D. Cole
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Heart Disease ◽  
Cell Therapy ◽  
Stem Cell Therapy ◽  
Autologous Bone Marrow ◽  
Autologous Bone

Abstract 003: Progenitor Cells Suppress T-Lymphocyte Proliferation Via a Paracrine Mechanism

2013 ◽  
Vol 113 (suppl_1) ◽  
Author(s):  
Frederieke van den Akker ◽  
Krijn R Vrijsen ◽  
Janine C Deddens ◽  
Pieter A Doevendans ◽  
Joost P Sluijter
Keyword(s):  
Stem Cell ◽  
T Lymphocytes ◽  
Cell Therapy ◽  
T Lymphocyte ◽  
Stem Cell Therapy ◽  
Lymphocyte Proliferation ◽  
Paracrine Factors ◽  
T Lymphocyte Proliferation ◽  
Dose Dependent Fashion ◽  
Dose Dependent

PURPOSE: Limited treatment options are available for heart failure patients. Stem cell therapy has recently become a potential new way of repairing injured cardiac tissue. Different progenitor cell sources have been investigated, but most promising for cardiac therapy are mesenchymal stem cells (MSC) and cardiomyocyte progenitor cells (CMPC). Cardiac stem cell therapy using MSC or CMPC improved cardiac function, despite low engraftment of the cells. Paracrine factors, produced by the injected cells, presumably cause these improvements. Many studies are performed on the paracrine effects, yet modulation of the immune response in cardiac stem cell therapy, especially the strong influence of T-lymphocytes on adverse remodeling, has not been explored extensively. Methods: Human fetal MSC and CMPC were characterized and tested for multipotency. The immunosuppressive properties of both cell types were tested in co-culture with allogeneic peripheral blood mononuclear cells (PBMC) or T-lymphocytes stimulated with IL-2 and PMA. Proliferation was measured by CFSE-analysis using flow cytometry. Results: Proliferation of PBMC and T-lymphocytes was significantly reduced in the presence of MSC (65 ± 8%) or CMPC (97 ± 0.6%). In addition, production of inflammatory cytokines IFN-gamma and TNF-alpha was strongly downregulated. This effect was observed in both direct cell contact as well as in transwell co-culture systems (MSC: 58 ± 10%; CMPC: 62 ± 9%). Transfer of conditioned medium from these co-cultures to unrelated, activated PBMC or T-lymphocytes abrogated proliferation in these cells to a similar extent as the original co-culture (MSC: 51 ± 8%; CMPC: 97 ± 0.7%). Interestingly, exosomes isolated from the conditioned medium of MSC and CMPC prevented T-lymphocyte proliferation in a dose-dependent fashion. At a concentration of 1.5μg, T-lymphocyte proliferation was significantly suppressed (MSC-exosomes: 73 ± 12%; CMPC-exosomes: 77 ± 10%). Conclusion: Both MSC and CMPC have a strong capacity for in vitro immunosuppression, which is mediated by paracrine factors. One potent immunosuppressive factor secreted by both MSC and CMPC are exosomes, which prevented T-lymphocyte proliferation in a dose-dependent fashion.

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