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

dc.contributor.author

Chinnadurai, Raghavan

dc.contributor.author

Copland, Ian B

dc.contributor.author

Garcia, Marco A

dc.contributor.author

Petersen, Christopher T

dc.contributor.author

Lewis, Christopher N

dc.contributor.author

Waller, Edmund K

dc.contributor.author

Kirk, Allan D

dc.contributor.author

Galipeau, Jacques

dc.date.accessioned

2020-07-14T07:36:33Z

dc.date.available

2020-07-14T07:36:33Z

dc.date.issued

2016-09

dc.date.updated

2020-07-14T07:36:32Z

dc.description.abstract

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.

dc.identifier.issn

1066-5099

dc.identifier.issn

1549-4918

dc.identifier.uri

https://hdl.handle.net/10161/21185

dc.language

eng

dc.publisher

Oxford University Press (OUP)

dc.relation.ispartof

Stem cells (Dayton, Ohio)

dc.relation.isversionof

10.1002/stem.2415

dc.subject

Lung

dc.subject

T-Lymphocytes

dc.subject

T-Lymphocytes, Cytotoxic

dc.subject

Mesenchymal Stem Cells

dc.subject

Animals

dc.subject

Mice, Inbred C57BL

dc.subject

Humans

dc.subject

Caspases

dc.subject

Cryopreservation

dc.subject

Immunosuppression

dc.subject

Lymphocyte Activation

dc.subject

Cell Communication

dc.subject

Apoptosis

dc.subject

Cell Proliferation

dc.subject

Cell Survival

dc.subject

Cell Degranulation

dc.subject

Heat-Shock Response

dc.subject

Freezing

dc.subject

Autophagy

dc.subject

Interferon-gamma

dc.subject

Polymerization

dc.title

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

dc.type

Journal article

duke.contributor.orcid

Lewis, Christopher N|0000-0002-5238-3774

duke.contributor.orcid

Kirk, Allan D|0000-0003-2004-5962

pubs.begin-page

2429

pubs.end-page

2442

pubs.issue

9

pubs.organisational-group

School of Medicine

pubs.organisational-group

Duke Cancer Institute

pubs.organisational-group

Immunology

pubs.organisational-group

Pediatrics

pubs.organisational-group

Surgery, Abdominal Transplant Surgery

pubs.organisational-group

Duke

pubs.organisational-group

Institutes and Centers

pubs.organisational-group

Basic Science Departments

pubs.organisational-group

Clinical Science Departments

pubs.organisational-group

Surgery

pubs.organisational-group

Staff

pubs.publication-status

Published

pubs.volume

34

Files

Original bundle

Now showing 1 - 1 of 1
Loading...
Thumbnail Image
Name:
2015 Lewis Kirk.pdf
Size:
1.15 MB
Format:
Adobe Portable Document Format