scholarly journals Co-infusion of autologous adipose tissue derived insulin-secreting mesenchymal stem cells and bone marrow derived hematopoietic stem cells: Viable therapy for type III.C. a diabetes mellitus

2013 ◽  
Vol 36 (6) ◽  
pp. 304 ◽  
Author(s):  
UmangG Thakkar ◽  
ArunaV Vanikar ◽  
HargovindL Trivedi
2018 ◽  
Vol 5 (1) ◽  
Author(s):  
Phuc Van Pham ◽  
Ngoc Bich Vu ◽  
Van Hong Tran

Introduction: Adipose-derived stem cells (ADSCs) are considered as mesenchymal stem cells (MSCs). Indeed, they display all characteristics of MSCs that compliant with the minimal criteria of MSCs suggested by Domonici et al. (2006). However, some recent studies showed that ADSCs contain the subpopulation that was positive with CD34 marker – a marker of hematopoietic stem cells. This study aimed to analyze and determine the expression of CD34 marker in ten samples of ADSCs obtained from 10 donors. Methods: All ADSC samples were isolated and expanded according to the published previous protocols. They were confirmed as the MSCs with some markers and differentiation potential, excepting the CD34 expression. Then they were cultured and analyzed the expression of CD34 by flow cytometry at passage 3, 5, 7 and 9. Results: The results showed that expression of CD34 in ADSCs was different between donors and their passages that accounted from 1.21% to 23.38%. Conclusion: These results suggested that ADSCs are not ‘truly” MSCs like MSCs from bone marrow.


Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2563-2563
Author(s):  
Fernando Fierro ◽  
Thomas Illmer ◽  
Duhoui Jing ◽  
Philip Le Coutre ◽  
Gerhard Ehninger ◽  
...  

Abstract Recent data show that the tyrosine kinase inhibitor Imatinib mesylate (IM) also affects normal hematopoietic stem cells (HSC), T lymphocyte activation and dendritic cell function not relying on the specific inhibition of bcr-abl activity. Mesenchymal stem cells (MSC) have been identified in the bone marrow (BM) as multipotent non-hematopoietic progenitor cells that differentiate into osteoblasts, adipocytes, chondrocytes, tenocytes, skeletal myocytes, and cells of visceral mesoderm. MSC interact with HSC, influencing their homing and differentiation through cell-cell contact and the production of factors including chemokines We evaluated possible effects of IM in vitro on human bone marrow-derived MSC. Screening the activity of fourty-two receptor tyrosine kinases by a phospho-receptor tyrosine kinase (RTK)-array revealed an exclusive inhibition of platelet-derived growth factor receptor (PDGFRβ) by IM which consequently affects downstream targets of PDGFRβ as Akt and Erk1/2 signalling pathways in a concentration and time dependent manner. Furthermore, perinuclear multivesicular bodies harbouring PDGFRβ were found within 18–20 hours culture of MSC in the presence of 5 μM IM. Cell proliferation and clonogenicity (evaluated as the capability to form colony forming units - fibroblasts (CFU-F)) of MSC were significantly inhibited by IM in a concentration dependent fashion. IM inhibits significantly the differentiation process of MSC into osteoblasts as evaluated by decreased alkaline phosphatase activity and reduced calcium phosphate precipitates. In contrary, differentiation of MSC into adipocytes was strongly favoured in presence of IM. All these functional deficits described, probably contribute to an observed 50% reduction in the support of clonogenic hematopoietic stem cells, as evaluated by a long term culture-initiating cells (LTC-IC)-based assay. In summary our experiments show that IM inhibits the capacity of human MSC to proliferate and to differentiate into the osteogenic lineage, favouring adipogenesis. This effect is mainly mediated by an inhibition of PDGFRβ autophosphorylation leading to a more pronounced inhibition of PI3K/Akt compared to Erk1/2 signalling. This work confirms the role of PDGFRβ recently described for the proliferation and differentiation potential of MSC and provides a first possible explanation for the altered bone metabolism found in certain patients treated with IM.


Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3650-3650
Author(s):  
Kent W. Christopherson ◽  
Tiki Bakhshi ◽  
Shamanique Bodie ◽  
Shannon Kidd ◽  
Ryan Zabriskie ◽  
...  

Abstract Hematopoietic Stem Cells (HSC) are routinely obtained from bone marrow, mobilized peripheral blood, and umbilical Cord Blood. Traditionally, adult bone marrow has been utilized as a source of Mesenchymal Stem Cells (MSC). Bone marrow derived MSC (BM-MSC) have previously been shown to maintain the growth of HSC obtained from cord blood and have been utilized for cord blood expansion purposes. However, the use of a mismatched BM-MSC feeder stromal layer to support the long term culture of cord blood HSC is not ideal for transplant purposes. The isolation of MSC from a novel source, the Wharton’s Jelly of Umbilical Cord segments, was recently reported (Romanov Y, et al. Stem Cells.2003; 21: 105–110) (Lee O, et al. Blood.2004; 103: 1669–1675). We therefore hypothesized that Umbilical Cord derived MSC (UC-MSC) have the ability to support the long term growth of cord blood derived HSC similar to that previously reported for BM-MSC. To test this hypothesis, MSC were isolated from the Wharton’s Jelly of Umbilical Cord segments and defined morphologically and by cell surface markers. UC-MSC were then tested for their ability to support the growth of pooled CD34+ cord blood cells in long term culture - initiating cell (LTC-IC) assays as compared to BM-MSC. We observed that like BM-MSC, CB-MSC express a defined set of cell surface markers. By flow cytometry we determined that that both UC-MSC and BM-MSC are positive for CD29, CD44, CD73, CD90, CD105, CD166, HLA-A and negative for CD45, CD34, CD38, CD117, HLA-DR expression. Utilizing Mitomycin C treated (200 μM, 15 min.) UC-MSC from multiple donors as a feeder layer we observed that UC-MSC have the ability to support the maintenance of long term hematopoiesis during the LTC-IC assay. Specifically, UC-MSC isolated from separate umbilical cord donors support the growth of 69.6±11.9 (1A), 31.7±3.9 (2B), 67.0±13.5 (3A), and 38.5±13.7 (3B) colony forming cells (CFC) per 1×104 CD34+ cord blood cells as compared to 64.0±4.2 CFC per 1×104 CD34+ cord blood cells supported by BM-MSC (Mean±SEM, N=4 separate segments from three different donors). Thus, Umbilical Cord derived Mesenchymal Stem Cells, a recently described novel source of MSC, have the ability to support long term maintenance of Hematopoietic Stem Cells, as defined by the LTC-IC assay. These results may have potential therapeutic application with respect to ex vivo stem cell expansion of Cord Blood Hematopoietic Stem Cells utilizing a Mesenchymal Stem Cell stromal layer. In addition, these data suggest the possibility of co-transplantation of matched Mesenchymal and Hematopoietic Stem Cells from the same umbilical cord and cord blood donor respectively. Lastly, these results describe a novel model system for the future study of the interaction between Cord Blood Hematopoietic Stem Cells and the appropriate supportive microenvironment represented by the Umbilical Cord - Mesenchymal Stem Cells.


2020 ◽  
Author(s):  
Yanan Kong ◽  
Liuhanghang Cheng ◽  
Min Xuan ◽  
Hao Ding ◽  
Biao Cheng

Abstract Background Hematopoietic stem cells(HSCs) and mesenchymal stem cells(MSCs) can participate in wound healing. However, very few studies had shown HSCs and MSCs could arrive to the wound and differentiate into tissues. In this study, we intend to investigate the role of bone marrow HSCs and MSCs in wound healing. Methods We first removed the bone marrow of mice by irradiation. Furthermore, we injected different colours of fluorescent HSCs and MSCs into the tail vein of irradiated mice to reconstruct bone marrow function. We prepared wound models on the back of these mice. In vivo imaging and immunohistochemical staining were used to track the expression of fluorescent protein. Results HSCs and MSCs have been isolated and cultured. HSCs expressed expressed Sca1, not lineage, CD34 or CD48. MSCs expressed expressed CD29 and CD44,not CD34 or CD45. HSCs labeled with green fluorescent protein reached the wound and co-expressed with desmin and α-SMA. MSCs didn’t stay on the wound. Conclusions The results show HSCs in the bone marrow of mice can directly participate in wound healing and differentiate into pericytes and myofibroblasts.


Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4045-4045
Author(s):  
Ferda Tekinturhan ◽  
Ludovic Zimmerlin ◽  
Vera S. Donnenberg ◽  
Melanie E. Pfeifer ◽  
Darlene A. Monlish ◽  
...  

Abstract Bone marrow (BM) contains hematopoietic stem cells (HSCs), which can give rise to all mature blood cells and marrow stromal cells as well. Recently, it has been shown that non-hematopoietic stem/progenitor cells which can differentiate into non-hematopoietic tissues also reside in the BM. Although culture expanded cells have been studied in great detail, little is known about the phenotype and quantity of these cells in freshly harvested adult human BM. The aim of this study is to isolate and characterize hematopoietic and non-hematopoietic stem/progenitor cells in adult human BM by comparing two different isolation techniques and their effects on the yield of hematopoietic, mesenchymal and endothelial stem/progenitor cell populations. BM samples were collected mechanically from isolated rib specimens obtained during lung resection (n=10), or from BM aspirates harvested from the humerus of orthopedic patients (n=17). BM mononuclear cells were purified on a Ficoll/Hypaque density gradient and stained simultaneously using CD105 FITC, CD73 PE, CD34 ECD, CD90 PE.Cy5, CD117 PE.Cy7, CD133 APC, CD45 APC.Cy7 and DAPI as a marker of nucleated cells. 2–15 million cells per sample were acquired on a Dako CyAn cytometer and the data were analyzed offline using prototype analytical software (Venturi, Applied Cytometry Systems). The significant difference in the percentage of the CD45 − singlets (non-hematopoietic cells) between BM aspirates and rib-derived samples indicates hemodilution in the bone marrow aspirates. Although we have observed a slight difference in the mean of hematopoietic stem cell content between samples, it was not statistically significant. According to our results, the quantity of mesenchymal stem cells was higher in rib-derived BM than BM aspirates (p value=0.028). The expression of some stem/progenitor cell markers, such as CD90 (Thy-1), CD117 (c-Kit) and CD133 remained similar for all cell types. Our results are shown in the table below. Surface Antigens RibBM (n=10)¥ BMA (n=17)¥ p Value % % Total Cells CD45- of nucleated cells 15.3 ± 7.9 5.7 ± 5.2 0.004 CD34+ Hematopoietic Stem Cells (HSCs)* CD34 of CD45+ 1.7 ± 1.48 2.6 ± 2.0 0.883 CD117 74.6 ± 31.3 53.3 ± 18.8 0.073 CD90 60.3 ± 44.5 35.9 ± 36.5 0.134 CD133 70.3 ± 31.8 62.3 ± 21.4 0.443 Endothelial Progenitor Cells (EPCs)* EPCs of nucleated cells 0.05 ± 0.03 0.12 ± 0.2 0.323 CD117 81.3 ± 29.8 78.1 ± 20.2 0.746 CD90 66.7 ± 39.7 53.7 ± 31.4 0.356 CD133 45.9 ± 32.7 33.9 ± 22.0 0.265 Mesenchymal Stem Cells (MSCs)* MSCs of nucleated cells 0.086 ± 0.14 0.008 ± 0.01 0.028 CD117 60.2 ± 36.8 49.8 ± 34.3 0.471 CD90 66.0 ± 27.7 65.7 ± 29.1 0.981 CD133 37.8 ± 27.4 39.9 ± 28.9 0.857 RibBM: Rib-derived BM, BMA: Bone Marrow Aspirate ¥Data are given as mean ± SD. *CD90, CD117 and CD133 expressions are shown for each stem/progenitor fraction: Hematopoietic stem cells (CD34 + CD45 + and light scatter properties according to the ISHAGE protocol), endothelial progenitor cells (CD34bright CD45 − CD105 +) and mesenchymal stem cells (CD34 − CD45 − CD73 + CD105 +).


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