Official Sections CTRMS ISVCA IPITA IPTA ISODP IRTA IXA SPLIT TID

2011 - CTS-IXA


This page contains exclusive content for the member of the following sections: TTS, CTS, IXA

Parallel Session 2- Stem Cells (Cell Track)

4.118 - Contact-dependent modulation of the human immune response to pig cells by adipose-derived mesenchymal stem cells (AdMSC) from GTKO/CD46 pigs

Presenter: Goutham, Kumar, Pittsburgh, United States
Authors: Goutham Kumar1, Hidetaka Hara1, Cassandra Long1, David Ayares2, David K.C. Cooper1, Mohamed Ezzelarab1

118

Contact-dependent modulation of the human immune response to pig cells by adipose-derived mesenchymal stem cells (AdMSC) from GTKO/CD46 pigs

Goutham Kumar1, Hidetaka Hara1, Cassandra Long1, David Ayares2, David K.C. Cooper1, Mohamed Ezzelarab1

1Thomas E. Starzl Transplantation Institute, Pittsburgh, PA; 2Revivicor Inc., Blacksburg, VA, United States

Introduction: The immunomodulatory and anti-inflammatory effects of MSC could prove to be a potential therapeutic approach for prolongation of survival of cell xenotransplantation. Genetically-modified pigs could be an abundant source of organs and cells, but also of donor-specific MSC.

Methods: pMSC were isolated from adipose tissue of α1, 3-galactosyltransferase gene knock-out pigs transgenic for human (h) CD46 [GTKO/hCD46]). pMSC were identified by differentiation and by surface phenotype by flowcytometry (FCM). Naïve human and sensitized baboon IgM/IgG binding to GTKO/hCD46 pAdMSC and GTKO pig aortic endothelial cells (pAEC) was measured by FCM. The immunomodulation of human peripheral blood mononuclear cell (PBMC) responses to GTKO pAEC by GTKO/hCD46 pAdMSC was compared with commercially-available hAdMSC by measuring 3H-thymidine uptake. The supernatants from the MSC cultures were used to determine the role of soluble factors.

Results: GTKO/hCD46 pAdMSC (i) did not express Galα1, 3Gal (Gal), but expressed hCD46, (ii) differentiated into chondroblasts, osteoblasts and adipocytes, (iii) expressed CD29, CD44, CD90, and CD105, but did not express CD45 or CD31, (iv) expressed lower levels of SLA I and II than pAEC before and after pIFN-γ stimulation (p<0.001), and (v) expressed costimulatory molecules (CD80, CD86) constitutively. Naïve human and sensitized baboon antibody binding to GTKO pAEC was greater than to GTKO/hCD46 pAdMSC. The proliferation of human PBMC to GTKO/hCD46 pAdMSC and hAdMSC stimulators was similar, and both were significantly lower than to GTKO pAEC (p<0.05). Human PBMC proliferation to GTKO pAEC was equally suppressed by GTKO/hCD46 pAdMSC and hAdMSC (p<0.01). The supernatant from GTKO/hCD46 pAdMSC did not suppress the human xenoresponse to GTKO pAEC.

Conclusions: (1) Genetically-modified pAdMSC are less immunogenic than GTKO pAEC, and no more immunogenic than hAdMSC. (2) The immunomodulatory function of pAdMSC is comparable to that of hAdMSC and is contact-dependent. (3) Genetically-modified pMSC may provide a potential therapy in cell xenotransplantation.


Important Disclaimer

By viewing the material on this site you understand and accept that:

  1. The opinions and statements expressed on this site reflect the views of the author or authors and do not necessarily reflect those of The Transplantation Society and/or its Sections.
  2. The hosting of material on The Transplantation Society site does not signify endorsement of this material by The Transplantation Society and/or its Sections.
  3. The material is solely for educational purposes for qualified health care professionals.
  4. The Transplantation Society and/or its Sections are not liable for any decision made or action taken based on the information contained in the material on this site.
  5. The information cannot be used as a substitute for professional care.
  6. The information does not represent a standard of care.
  7. No physician-patient relationship is being established.

Social

Contact

Staff Directory
+1-514-874-1717
This email address is being protected from spambots. You need JavaScript enabled to view it.

Address

The Transplantation Society
International Headquarters
505 Boulevard René-Lévesque Ouest
Suite 1401
Montréal, QC, H2Z 1Y7
Canada