scholarly journals Human mesenchymal stem cell sheets in xeno-free media for possible allogenic applications

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Kyungsook Kim ◽  
Sophia Bou-Ghannam ◽  
Hallie Thorp ◽  
David W. Grainger ◽  
Teruo Okano

Abstract Cell-based therapies are increasingly focused on allogeneic stem cell sources because of several advantages in eliminating donor variability (e.g., aging and disease pathophysiology) affecting stem cell quality and in cell-banked sourcing of healthy donors to enable “off-the-shelf” products. However, allogeneic cell therapy is limited by host patient immunologic competence and inconsistent performance due to cell delivery methods. To address allogeneic cell therapy limitations, this study developed a new allogeneic stem cell sheet using human umbilical cord mesenchymal stem cells (hUC-MSC) that present low antigenicity (i.e., major histocompatibility complex, MHC). Optimal conditions including cell density, passage number, and culture time were examined to fabricate reliable hUC-MSC sheets. MHC II antigens correlated to alloimmune rejection were barely expressed in hUC-MSC sheets compared to other comparator MSC sheets (hBMSC and hADSC). hUC-MSC sheets easily graft spontaneously onto subcutaneous tissue in immune-deficient mice within 10 minutes of placement. No sutures are required to secure sheets to tissue because sheet extracellular matrix (ECM) actively facilitates cell-target tissue adhesion. At 10 days post-transplantation, hUC-MSC sheets remain on ectopic target tissue sites and exhibit new blood vessel formation. Furthermore, implanted hUC-MSC sheets secrete human HGF continuously to the murine target tissue. hUC-MSC sheets described here should provide new insights for improving allogenic cell-based therapies.

2001 ◽  
Vol 7 (4) ◽  
pp. 230-238 ◽  
Author(s):  
David L Porter ◽  
Selina M Luger ◽  
Kathleen M Duffy ◽  
Edward A Stadtmauer ◽  
Ginna Laport ◽  
...  

2014 ◽  
Vol 115 (suppl_1) ◽  
Author(s):  
Jong-Ho Kim ◽  
Hyung Joon Joo ◽  
Ha-Rim Seo ◽  
Long-Hui Cui ◽  
Mi-Na Kim ◽  
...  

Background: Cell sheet technology has magnified as an important transplantation skill. Mouse adipose derived stem cells (mADSCs) can secrete various growth factors, which promote the repair of damaged cardiomyocyte and protecting cells from death. In addition, autologous cell source to easily obtain from patients are promising candidates for cell therapy in cardiovascular field. Methods: mADSCs were confirmed stem cell properties and secreted cytokines were evaluated in vitro. Eighteen acute myocardial infarction (AMI) rats were divide into 3 group; sham (n=6), suspended mADSCs (n=6), and mADSCs sheet (n=6) groups. In the mADSCs sheet group, 60х106 cells were cultured for 2 days onto temperature-responsive polymers and the sheets were then transplanted over the infarct region. In additional, the sheet was made of carboxyfluorescein diacetate succinimidyl ester (CFDA) -labelled mADSCs to confirmed cell survival. Engraftment and differentiation were blindly assessed after 28 days. Results: The mADSCs expressed Sca-1+ and represented multi-differentiation potential. Interestingly, EGF and IGF levels significantly increased in the mADSCs sheet. Significant improvements in ejection fraction and fraction shortening value were observed in the mADSCs sheet and suspended mADSCs groups compared with the sham group at 14 and 28 days. But, it was not higher significance level in the mADSCs sheet group than in the suspended mADSCs group. Engraftment range and fibrosis area of infarct region were significantly higher in the mADSCs sheet group compared to the other two groups at 4, 14 and 28 days. In significant expressed cytokines (bFGF, IL-1a, IL-1ra, CT-1, EGF, TGFb1, IGF-1, IGF-2 and MCP-1) were observed in the mADSCs sheet group compared with the other 2 groups at 28 days after transplantation. In addition, in the mADSCs sheet was confirmed endothelial differentiation by Von Willebrand factor (vWF) at 4, 14 and 28 days. Conclusions: Transplantation of mADSCs sheet into rat infarcted myocardium increased engraftment and survival of transplanted cells. The mADSCs sheet is very useful for the study of stem cell proliferation and differentiation as well as for cell therapy in cardiovascular field.


Circulation ◽  
2012 ◽  
Vol 125 (1) ◽  
pp. 100-112 ◽  
Author(s):  
Konstantinos Malliaras ◽  
Tao-Sheng Li ◽  
Daniel Luthringer ◽  
John Terrovitis ◽  
Ke Cheng ◽  
...  

2015 ◽  
Vol 5 (3) ◽  
pp. 342-352 ◽  
Author(s):  
Lijun Zhang ◽  
Qi Xing ◽  
Zichen Qian ◽  
Mitchell Tahtinen ◽  
Zhaoqiang Zhang ◽  
...  

2013 ◽  
Vol 34 (suppl 1) ◽  
pp. P1462-P1462
Author(s):  
S. J. Jansen Of Lorkeers ◽  
J. E. C. Eding ◽  
T. I. G. Van Der Spoel ◽  
H. M. Vesterinen ◽  
S. Koudstaal ◽  
...  

Stroke ◽  
2016 ◽  
Vol 47 (suppl_1) ◽  
Author(s):  
Amin Adibi ◽  
Arindom Sen ◽  
Alim P Mitha

Introduction: Recurrence of intracranial aneurysms following endovascular therapy in 20% of patients remains the only major disadvantage of this treatment. For this reason, a significant amount of research has been carried out, focused on reducing the incidence of recurrence. In recent years, a variety of cell therapy modalities using fibroblasts, smooth muscle cells, endothelial progenitor cells and Mesenchymal Stem/Stromal Cells (MSCs) have been tested in animal models as a means to improve the outcome of the treatment. However, it remains unclear whether preventing recurrence using cell therapy is a more cost-effective alternative to retreating recanalized aneurysms. In this study, we have used a Markov model approach to determine efficacy thresholds at which combined coiling and cell therapy becomes a more cost-effective treatment than coiling alone. Hypothesis: Combined coiling and cell therapy will be more cost-effective than coiling alone, if it reduces the need for retreatment by 50% or more. Methods: The cell therapy was assumed to be aimed at reducing the need for retreatment. A Markov model was used to compare coiling alone with combined coiling and autologous/allogeneic cell therapy. Model inputs were mostly taken from meta-analyses. Sensitivity analysis was performed to predict efficacy thresholds that make cell therapy more cost-effective than coiling alone. Robustness of the model was assessed through further sensitivity testing focused on variables with the highest impact on the outcome. Results: Sensitivity analysis showed that coiling with autologous cell therapy becomes more cost-effective than coiling alone, if it reduces the need for retreatment by 39.9% or more. When allogeneic cell are used, a reduction of 13.3% or more in the need for retreatment is enough the make combined coiling and cell therapy more cost-effective. Conclusions: Our preliminary analysis suggests that efficacy thresholds at which combined coiling and cell therapy becomes more cost-effective than coiling alone are modest - especially for allogeneic MSC therapies. This makes combined coiling and cell therapy a viable alternative to the current standard-of-care from a cost-utility standpoint, and justifies further research and investment in the field.


2020 ◽  
Vol 26 (13-14) ◽  
pp. 792-810
Author(s):  
Zhina Sadeghi ◽  
Jonathan D. Kenyon ◽  
Brian Richardson ◽  
Ahmad O. Khalifa ◽  
Michael Cartwright ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document