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Cryopreserved Mesenchymal Stromal Cells Are Susceptible to T-Cell Mediated Apoptosis Which Is Partly Rescued by IFNγ Licensing.

Publication ,  Journal Article
Chinnadurai, R; Copland, IB; Garcia, MA; Petersen, CT; Lewis, CN; Waller, EK; Kirk, AD; Galipeau, J
Published in: Stem Cells
September 2016

We have previously demonstrated that cryopreservation and thawing lead to altered Mesenchymal stromal cells (MSC) functionalities. Here, we further analyzed MSC's fitness post freeze-thaw. We have observed that thawed MSC can suppress T-cell proliferation when separated from them by transwell membrane and the effect is lost in a MSC:T-cell coculture system. Unlike actively growing MSCs, thawed MSCs were lysed upon coculture with activated autologous Peripheral Blood Mononuclear Cells (PBMCs) and the lysing effect was further enhanced with allogeneic PBMCs. The use of DMSO-free cryoprotectants or substitution of Human Serum Albumin (HSA) with human platelet lysate in freezing media and use of autophagy or caspase inhibitors did not prevent thaw defects. We tested the hypothesis that IFNγ prelicensing before cryobanking can enhance MSC fitness post thaw. Post thawing, IFNγ licensed MSCs inhibit T cell proliferation as well as fresh MSCs and this effect can be blocked by 1-methyl Tryptophan, an Indoleamine 2,3-dioxygenase (IDO) inhibitor. In addition, IFNγ prelicensed thawed MSCs inhibit the degranulation of cytotoxic T cells while IFNγ unlicensed thawed MSCs failed to do so. However, IFNγ prelicensed thawed MSCs do not deploy lung tropism in vivo following intravenous injection as well as fresh MSCs suggesting that IFNγ prelicensing does not fully rescue thaw-induced lung homing defect. We identified reversible and irreversible cryoinjury mechanisms that result in susceptibility to host T-cell cytolysis and affect MSC's cell survival and tissue distribution. The susceptibility of MSC to negative effects of cryopreservation and the potential to mitigate the effects with IFNγ prelicensing may inform strategies to enhance the therapeutic efficacy of MSC in clinical use. Stem Cells 2016;34:2429-2442.

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Published In

Stem Cells

DOI

EISSN

1549-4918

Publication Date

September 2016

Volume

34

Issue

9

Start / End Page

2429 / 2442

Location

England

Related Subject Headings

  • T-Lymphocytes, Cytotoxic
  • T-Lymphocytes
  • Polymerization
  • Mice, Inbred C57BL
  • Mesenchymal Stem Cells
  • Lymphocyte Activation
  • Lung
  • Interferon-gamma
  • Immunosuppression Therapy
  • Immunology
 

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Chinnadurai, R., Copland, I. B., Garcia, M. A., Petersen, C. T., Lewis, C. N., Waller, E. K., … Galipeau, J. (2016). Cryopreserved Mesenchymal Stromal Cells Are Susceptible to T-Cell Mediated Apoptosis Which Is Partly Rescued by IFNγ Licensing. Stem Cells, 34(9), 2429–2442. https://doi.org/10.1002/stem.2415
Chinnadurai, Raghavan, Ian B. Copland, Marco A. Garcia, Christopher T. Petersen, Christopher N. Lewis, Edmund K. Waller, Allan D. Kirk, and Jacques Galipeau. “Cryopreserved Mesenchymal Stromal Cells Are Susceptible to T-Cell Mediated Apoptosis Which Is Partly Rescued by IFNγ Licensing.Stem Cells 34, no. 9 (September 2016): 2429–42. https://doi.org/10.1002/stem.2415.
Chinnadurai R, Copland IB, Garcia MA, Petersen CT, Lewis CN, Waller EK, et al. Cryopreserved Mesenchymal Stromal Cells Are Susceptible to T-Cell Mediated Apoptosis Which Is Partly Rescued by IFNγ Licensing. Stem Cells. 2016 Sep;34(9):2429–42.
Chinnadurai, Raghavan, et al. “Cryopreserved Mesenchymal Stromal Cells Are Susceptible to T-Cell Mediated Apoptosis Which Is Partly Rescued by IFNγ Licensing.Stem Cells, vol. 34, no. 9, Sept. 2016, pp. 2429–42. Pubmed, doi:10.1002/stem.2415.
Chinnadurai R, Copland IB, Garcia MA, Petersen CT, Lewis CN, Waller EK, Kirk AD, Galipeau J. Cryopreserved Mesenchymal Stromal Cells Are Susceptible to T-Cell Mediated Apoptosis Which Is Partly Rescued by IFNγ Licensing. Stem Cells. 2016 Sep;34(9):2429–2442.
Journal cover image

Published In

Stem Cells

DOI

EISSN

1549-4918

Publication Date

September 2016

Volume

34

Issue

9

Start / End Page

2429 / 2442

Location

England

Related Subject Headings

  • T-Lymphocytes, Cytotoxic
  • T-Lymphocytes
  • Polymerization
  • Mice, Inbred C57BL
  • Mesenchymal Stem Cells
  • Lymphocyte Activation
  • Lung
  • Interferon-gamma
  • Immunosuppression Therapy
  • Immunology