Mesenchymal Stem Cells are of Recipient Origin in Pediatric Transplantations Using Umbilical Cord Blood, Peripheral Blood, or Bone Marrow

2007 ◽  
Vol 29 (6) ◽  
pp. 388-392 ◽  
Author(s):  
Javier Garc??a-Castro ◽  
Antonio Balas ◽  
Manuel Ram??rez ◽  
Antonio P??rez-Mart??nez ◽  
Luis Madero ◽  
...  
Blood ◽  
2006 ◽  
Vol 108 (10) ◽  
pp. 3360-3362 ◽  
Author(s):  
Karen M. Pastos ◽  
William B. Slayton ◽  
Lisa M. Rimsza ◽  
Linda Young ◽  
Martha C. Sola-Visner

Abstract Umbilical cord blood (CB) is a valuable source of stem cells for transplantation, but CB transplantations are frequently complicated by delayed platelet engraftment. The reasons underlying this are unclear. We hypothesized that CB- and peripheral-blood (PB)–derived megakaryocytes (MKs) respond differently to the adult hematopoietic microenvironment and to thrombopoietin (Tpo). To test this, we cultured CB- and PB-CD34+ cells in adult bone marrow stromal conditioned media (CM) or unconditioned media (UCM) with increasing concentrations of recombinant Tpo and compared the effects of these conditions on CB-versus PB-MKs. PB-MKs reached highest ploidy in response to UCM + 100 ng/mL rTpo, and the addition of CM inhibited their maturation. In contrast, CB-MKs reached highest ploidy in CM without rTpo, and high rTpo concentrations (> 0.1 ng/mL) inhibited their maturation. This is the first evidence that human neonatal and adult MKs have substantially different biologic responses to Tpo and potentially to other cytokines.


2008 ◽  
Vol 233 (7) ◽  
pp. 901-913 ◽  
Author(s):  
C. K. Rebelatto ◽  
A. M. Aguiar ◽  
M. P. Moretão ◽  
A. C. Senegaglia ◽  
P. Hansen ◽  
...  

2019 ◽  
Vol 2019 ◽  
pp. 1-17 ◽  
Author(s):  
Lélia Bertoni ◽  
Thomas Branly ◽  
Sandrine Jacquet ◽  
Mélanie Desancé ◽  
Loïc Desquilbet ◽  
...  

Osteoarthritis is a significant and costly cause of pain for both humans and horses. The horse has been identified as a suitable model for human osteoarthritis. Regenerative therapy with allogeneic mesenchymal stem cells (MSCs) is a promising treatment, but the safety of this procedure continues to be debated. The aim of this study is to evaluate the safety of intra-articular injections of allogeneic MSCs on healthy joints by comparing two different dosages and two different tissue sources, namely, bone marrow and umbilical cord blood, with a placebo treatment on the same individuals. We also assessed the influence of autologous versus allogeneic cells for bone marrow-derived MSC treatment. Twelve clinically sound horses were subjected to injections in their 4 fetlock joints. Each of the three fetlocks was administered a different MSC type, and the remaining fetlock was injected with phosphate-buffered saline as a control. Six horses received 10 million cells per joint, and the 6 other horses received 20 million cells per joint. Clinical and ultrasound monitoring revealed that allogeneic bone marrow-derived MSCs induced significantly more synovial effusion compared to umbilical cord blood-derived MSCs but no significant difference was noted within the synovial fluid parameters. The administration of 10 million cells in horses triggered significantly more inflammatory signs than the administration of 20 million cells. Mesenchymal stem cell injections induced mild to moderate local inflammatory signs compared to the placebo, with individual variability in the sensitivity to the same line of MSCs. Understanding the behavior of stem cells when injected alone is a step towards the safer use of new strategies in stem cell therapy, where the use of either MSC secretome or MSCs combined with biomaterials could enhance their viability and metabolic activity.


2020 ◽  
Author(s):  
Zhi Huang ◽  
Yuhua Xiao ◽  
Xiaomin Chen ◽  
Huiping Li ◽  
Jingyu Gao ◽  
...  

Abstract Background: Iron overload aggravates the difficulty of umbilical cord blood stem cell engraftment and reduces the survival of patients undergoing hematopoietic stem cells (HSC) transplantation. Mesenchymal stem cells (MSC) have been implicated in playing a significant role in HSC engraftment. This study aimed to determine the effect of intra-bone marrow (IBM) co-transplantation of umbilical cord blood mononuclear cells (UCB-MNC) and mesenchymal stem cells (UC-MSC) on the engraftment and hematopoietic recovery in an iron overload hematopoietic microenvironment. Methods: The iron overload model was established by dose-escalation intraperitoneal injection of iron dextran in NOD/SCID mice. Iron deposition in the bone marrow, heart, and liver was examined using H&E staining. Serum levels of ferritin and iron status in the liver were measured. The iron overload NOD/SCID mice were sublethally irradiated and divided into four groups for transplantation: (1) control group, (2) IBM MSC+ group: IBM injection of combined UCB-MNC/UC-MSC, (3) IBM group: IBM injection of only UCB-MNC, and (4) IV group: intravenous injection of UCB-MNC. Six weeks after transplantation, the human CD45 + cells in the bone marrow were analyzed by flow cytometry. The semi-quantitative analysis of vascular endothelial growth factor (VEGF-a), osteopontin (OPN), and stromal cell-derived factor-1a (SDF-1a) were examined by immunohistochemistry staining (IHC). Results: The survival rate and the percentages of human CD45 + cells in bone marrow were highest in the IBM MSC+ group with statistical significance. In addition, the levels of VEGF-a, OPN, and SDF-1a in bone marrow were all significantly higher in the IBM MSC+ group than the other groups. Conclusion: IBM co-transplantation of UC-MSC might improve the engraftment of UCB-MNC in iron overload NOD/SCID mice. The increased expression of VEGF-a, OPN, and SDF-1a in the bone marrow may be involved in improving the hematopoietic microenvironment and promoting the implantation of human umbilical cord blood stem cells in the bone marrow with iron overload.


Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2569-2569
Author(s):  
Robb Friedman ◽  
Monica Betancur ◽  
Hande Tuncer ◽  
Laurent Boissel ◽  
Curtis Cetrulo ◽  
...  

Abstract Umbilical cord blood (UCB) is a viable source of hematopoietic stem cells for transplantation of children and adults undergoing treatment for hematological malignancies. However only 4% of adults 70kg and over have a UCB unit available which contains the widely accepted minimum cell dose of 1.5x107 mononuclear cells per kilogram. Co-transplantation of hematopoietic stem cells with mesenchymal stem cells may enhance engraftment and therefore decrease transplant-related morbidity and mortality from delayed leukocyte recovery associated with a low pre-transplant cell dose. Umbilical cord matrix (UCM) cells, found in the Wharton’s Jelly, were easily and reliably extracted from minced pieces of cord by culture in RPMI + 20% fetal bovine serum at 37° and 5% humidified CO2. UCM expand best in 20% FBS but can also be expanded in human serum, autologous serum, and X-VIVO10. Small (1–3mm) minced pieces of umbilical cord can be cyropreserved at the time of delivery in 10% DMSO solution. UCM cells exhibit a fibroblast morphology and express markers common to mesenchymal stem cells: CD73 (SH3), CD105 (SH2), CD 29, CD44, CD49b, CD117, CD166, STRO-1 and HLA-DR. UCM are negative for CD14, CD 19, CD34, and CD45. Morphology and cell surface marker expression is stable after greater than fifteen passages. UCM cells grown in culture were shown to produce more GM-CSF and G-CSF than similar numbers of adult bone marrow mesenchymal stem cells, GM-CSF 178 pg/mL versus 77 pg/mL and G-CSF 82.6 pg/mL versus 7.9 pg/mL. NOD/SCID mice treated with anti-NK 1.1 antibodies and irradiated with 350 cGy were injected with suboptimal (1x104) numbers of cord blood CD34+ cells with and without 1x106 autologous UCM cells, extracted from the same umbilical cord as the cord blood CD34+ cells. Bone marrow was harvested at six weeks post transplant from both femurs and tibias and peripheral blood obtained via cardiac puncture. The percentage of human CD45+ cells in the bone marrow and the peripheral blood was assessed by flow cytometry. NOD/SCID mice transplanted with 1x104 cord blood CD34+ cells alone had 3.0% human CD45+ cell engraftment in the bone marrow and 3.6% human CD45+ cells in the peripheral blood, while NOD/SCID mice transplanted with 1x104 CD34+ cells and 1x106 UCM cells had an average of 27.3% human CD45+ cell engraftment in the bone marrow and 3.9% human CD45+ cells in the peripheral blood. These results indicate a trend towards improved engraftment in vivo with co-transplantation of suboptimal numbers of umbilical cord blood CD34+ cells and autologous umbilical cord matrix cells versus transplantation of suboptimal numbers of umbilical cord CD34+ cells alone.


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