Environmental manipulation to promote stem cell survival in vivo: use of aggregation, oxygen carrier, and BMP-2 co-delivery strategies

2016 ◽  
Vol 4 (20) ◽  
pp. 3594-3607 ◽  
Author(s):  
Ashley B. Allen ◽  
Josh A. Zimmermann ◽  
Olivia A. Burnsed ◽  
Doron Cohn Yakubovich ◽  
Hazel Y. Stevens ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cell Survival ◽  
Oxygen Carrier ◽  
Bone Defect Repair ◽  
Environmental Manipulation ◽  
Stem Cell Survival ◽  
Significant Barrier ◽  
Defect Repair ◽  
Delivery Strategies

While mesenchymal stem cell (MSC)-based strategies for critically-sized bone defect repair hold promise, poor cell survival in vivo remains a significant barrier to the translation of these therapeutics.

scholarly journals Serial in vivo imaging of transplanted allogeneic neural stem cell survival in a mouse model of amyotrophic lateral sclerosis

2017 ◽  
Vol 289 ◽  
pp. 96-102 ◽  
Author(s):  
Amit K. Srivastava ◽  
Sarah K. Gross ◽  
Akshata A. Almad ◽  
Camille A. Bulte ◽  
Nicholas J. Maragakis ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Stem Cell ◽  
Mouse Model ◽  
Cell Survival ◽  
Neural Stem Cell ◽  
In Vivo Imaging ◽  
Stem Cell Survival ◽  
Lateral Sclerosis

scholarly journals UFMylation of MRE11 is essential for maintenance of telomere length and hematopoietic stem cell survival

2019 ◽  
Author(s):  
Lara Lee ◽  
Ana Belen Perez Oliva ◽  
Dmitri Churikov ◽  
Elena Martinez-Balsalobre ◽  
Joshua Peter ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cell Survival ◽  
Telomere Length ◽  
Hematopoietic Stem Cell ◽  
Strand Break ◽  
Telomere Maintenance ◽  
Hematopoietic Stem ◽  
Telomere Protein ◽  
Stem Cell Survival

AbstractGenetic studies using knockout mouse models provide strong evidence for the essential role of the ubiquitin-like protein UFM1 for hematopoiesis, especially erythroid development, yet its biological roles in this process are largely unknown. Here we have identified a UFL1-dependent UFMylation of the MRE11 nuclease on the K281 and K282 residues. We show that Hela cells lacking the specific UFM1 E3 ligase display severe telomere shortening. We further demonstrate either by deleting UFM1 or by mutating MRE11 UFMylation sites that preventing MRE11 UFMylation impacts its interaction with the telomere protein TRF2. However, the MRE11 function in double-strand-break repair remains intact. We validate these results in vivo by showing that Zebrafish knockouts for the genes ufl1 and ufm1 have shorter telomeres in hematopoietic cells. Here we present UFMylation has a new mechanisms of regulation for telomere length maintenance with a role in hematopoiesis.Key pointsModification of MRE11 by UFM1 regulates telomere maintenance and cell death in HSCsScientific categoryUFMylation, telomere maintenance, hematopoietic stem cell survival.

Cultured Human Macrophages As a Model for Central Macrophages in Erythroblastic Islands

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 1248-1248
Author(s):  
Esther Heideveld ◽  
Maartje van Den Biggelaar ◽  
Floris P. van Alphen ◽  
Marieke Von Lindern ◽  
Emile van den Akker
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Cell Survival ◽  
Peripheral Blood ◽  
Human Bone ◽  
Hematopoietic Stem ◽  
Erythroblastic Island ◽  
Stem Cell Survival

Abstract Erythropoiesis occurs in erythroblastic islands, specific structures in the bone marrow comprising a central macrophage surrounded by erythroid precursors at different stages of terminal differentiation. The central macrophage of the erythroblastic island supports proliferation and differentiation of erythroblasts, as well as phagocytosis of the extruded erythroblast nuclei, the pyrenocytes. Its identity, however, has been poorly characterized. We previously showed that macrophages also enhance in vitro erythropoiesis because they support hematopoietic stem cell (HSC) survival [Heideveld et al. 2015]. Thus, bone marrow macrophages affect all stages of erythropoiesis. The aim of our study is to characterize the relevant human bone marrow macrophages and unravel the mechanism by which they support erythropoiesis with the ultimate goal (i) to optimize erythroblast culture systems that produce erythrocytes for transfusion purposes, and (ii) to target macrophages in vivo to improve erythropoiesis in anemic patients. Macrophages are a heterogeneous population, that can be divided into pro-inflammatory M1 and anti-inflammatory M2 macrophages. Macrophages that we showed to support stem cell survival, and subsequently enhance the yield of erythroid cell cultures, were characterized as a subclass: M2c-like macrophages. These macrophages were derived from CD14+ cells isolated from human peripheral blood mononuclear cells that were cultured in serum-free media supplemented with stem cell factor, erythropoietin and dexamethasone. Within three days these macrophages expressed CD163high, CD169, mannose receptor (MR), CXCR4 and HLA-DR and harbored characteristics of bone marrow resident macrophages. This differentiation process was dependent on glucocorticoid receptor activation. Mass spectrometry of monocytes cultured in presence and absence of dexamethasone showed that expression of CD163 and MR was strictly Dex-dependent, underscoring the role of glucocorticoids in the phenotype of M2c macrophages. Protein ontology analysis revealed dexamethasone-mediated enrichment of lysosome, endocytosis and endothelial development (e.g. STAB1, IL13RA1, CD81, SLC1A3 and FKBP5). We wondered whether these macrophages with increased endosomal and lysosomal capacity not only support stem cell survival and enable erythroid commitment, but also support erythroblastic islands. In mice, it has been shown that clearance of the pyrenocytes by central macrophages occurs presumably via TAM-receptors on the macrophages. Indeed, mRNA expression of cultured M2c-like macrophages showed increased levels of TAM family members MerTK and AXL. Functionally, these macrophages have the capacity to phagocytose zymosan and to bind nuclei. Furthermore, co-culture of the M2c-like macrophages with erythroblasts yielded GPA+(erythroid marker)/CD14+ cell aggregates that suggested the formation of erythroblastic islands. Interestingly, M2c-like macrophages expressing CD163high, MR and CD169 were also observed in human bone marrow aspirates and human fetal livers resembling macrophages induced in in vitro cultures in presence of dexamethasone. Currently, we investigate the mechanism by which glucocorticoids induce monocytes to differentiate into macrophages that may be used to model erythroblastic island-mediated erythropoiesis. Knowledge on the function of such a erythroblastic island is lacking by the absence of an in vitro model. Furthermore, targeting this mechanism in vivo may enhance the recovery of erythropoiesis following bone marrow transplantation. CD14+ cells from peripheral blood positively regulate hematopoietic stem and progenitor cell survival resulting in increased erythroid yield. (2015) Heideveld E, Masiello F, Marra M, Esteghamat F, Yağcı N, von Lindern M, Migliaccio AR, van den Akker E. Haematologica. 100(11):1396-1406 Disclosures No relevant conflicts of interest to declare.

Bcl-2 Overexpression Increases In Vivo Stem Cell Survival and Enhances Tissue Regeneration in Calvarial Defect Model

2013 ◽  
Vol 179 (2) ◽  
pp. 343
Author(s):  
J.S. Hyun ◽  
M.M. Grova ◽  
D.D. Lo ◽  
S.D. Morrison ◽  
H. Nejadnik ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cell Survival ◽  
Tissue Regeneration ◽  
Calvarial Defect ◽  
Defect Model ◽  
Stem Cell Survival

scholarly journals In vivo imaging and evaluation of different biomatrices for improvement of stem cell survival

2007 ◽  
Vol 1 (6) ◽  
pp. 465-468 ◽  
Author(s):  
Feng Cao ◽  
Amir H. Sadrzadeh Rafie ◽  
Oscar J. Abilez ◽  
Haichang Wang ◽  
Jennifer T. Blundo ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cell Survival ◽  
In Vivo Imaging ◽  
Stem Cell Survival

scholarly journals Mitochondria transfer enhances bone marrow mesenchymal stem cell functions and promotes bone defect healing

2020 ◽  
Author(s):  
Yusi Guo ◽  
Xiaopei Chi ◽  
Yifan Wang ◽  
Boon Chin Heng ◽  
Yan Wei ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Bone Defect ◽  
Atp Production ◽  
Bone Defect Repair ◽  
Mitochondria Transfer ◽  
Defect Repair

Abstract Background: Bone marrow-derived mesenchymal stem cells (BMSCs) transplantation is considered a promising therapeutic approach for bone defect repair. However, during the transplantation procedure, the functions and viability of BMSCs may be impaired due to extended durations of in vitro culture, aging and disease conditions of patients. Inspired by spontaneous intercellular mitochondria transfer that naturally occurs within injured tissues to rescue cellular or tissue function, we investigated whether artificial mitochondria transfer into pre-transplant BMSCs in vitro could improve cellular function and enhance their therapeutic effects on bone defect repair in situ. Methods: First, mitochondria were isolated from donor BMSCs and transferred into recipient BMSCs of the same passage. Afterwards, changes in proliferative capability was evaluated by Cell Counting Kit-8, Ki67 staining, etc., while Transwell, wound scratch healing and cell motility tests were conducted to determine migration ability. Then, alkaline phosphatase (ALP) staining, Alizarin Red staining, combined with qPCR and Western Blot experiments of Runx2 and BMP2 were performed to elucidate the effect of mitochondria transfer on the osteogenic potential of BMSCs in vitro. After that, the in vivo experiments were completed by transplanting mitochondria-recipient BMSCs into a rat cranial critical-size bone defect model. Micro CT scanning and histological analysis were conducted 4 weeks and 8 weeks after transplantation to evaluate the osteogenesis effect in situ. Finally, in order to discover the potential connection between cellular behavioral changes and aerobic metabolism, OXPHOS (oxidative phosphorylation) and ATP production were assessed and inhibition of aerobic respiration by oligomycin was proceeded. Results: Mitochondria-recipient BMSCs exhibited significantly enhanced proliferation and migration, and increased osteogenic differentiation upon osteogenic induction. The in vivo results showed more new bone formation after transplantation of mitochondria-recipient BMSCs in situ. Increased OXPHOS activity and ATP production were further observed, whereas the inhibition of which impaired the enhancement of proliferation, migration and osteogenic differentiation induced by mitochondria transfer. Conclusions: Mitochondria transfer is a feasible technique to enhance BMSCs function in vitro and promote bone defect repair in situ through the up-regulation of aerobic metabolism. The results indicated that mitochondria transfer may be a novel promising technique for optimizing stem cell function.

Enhancing stem cell survival in vivo for tissue repair

2013 ◽  
Vol 31 (5) ◽  
pp. 736-743 ◽  
Author(s):  
Jeong S. Hyun ◽  
Misha C. Tran ◽  
Victor W. Wong ◽  
Michael T. Chung ◽  
David D. Lo ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cell Survival ◽  
Tissue Repair ◽  
Stem Cell Survival
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