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Stem Cell Research and Therapy

, 6:222

First Online: 11 November 2015Received: 19 September 2014Revised: 20 September 2014Accepted: 29 October 2015

Abstract

IntroductionMesenchymal stem stromal cells MSCs possess self-renewal, differentiation and immunoregulatory properties, and therefore are being evaluated as cellular therapy for inflammatory and autoimmune diseases, and for tissue repair. MSCs isolated from bone marrow are extensively studied. Besides bone marrow, MSCs have been identified in almost all organs of the body including the lungs. Lung-derived MSCs may be more effective as therapy for lung diseases as compared to bone marrow-derived MSCs. Pigs are similar to humans in anatomy, physiology and immunological responses, and thus may serve as a useful large animal preclinical model to study potential cellular therapy for human diseases.

MethodsWe isolated MSCs from the lungs L-MSCs of 4–6-week-old germ-free pigs. We determined the self-renewal, proliferation and differentiation potential of L-MSCs. We also examined the mechanisms of immunoregulation by porcine L-MSCs.

ResultsMSCs isolated from porcine lungs showed spindle-shaped morphology and proliferated actively in culture. Porcine L-MSCs expressed mesenchymal markers CD29, CD44, CD90 and CD105 and lacked the expression of hematopoietic markers CD34 and CD45. These cells were multipotent and differentiated into adipocytes, osteocytes and epithelial cells. Like human MSCs, L-MSCs possessed immunoregulatory properties and inhibited proliferation of T cells and interferon-γ and tumor necrosis factor-α production by T cells and dendritic cells, respectively, and increased the production of T-helper 2 cytokines interleukin IL-4 and IL-13 by T cells. L-MSCs induced the production of prostaglandin E2 PGE2 in MSC–T cell co-cultures and inhibition of PGE2 significantly restored not completely the immune modulatory effects of L-MSCs.

ConclusionsHere, we demonstrate that MSCs can be isolated from porcine lung and that these cells, similar to human lung MSCs, possess in vitro proliferation, differentiation and immunomodulatory functions. Thus, these cells may serve as a model system to evaluate the contribution of lung MSCs in modulating the immune response, interactions with resident epithelial cells and tissue repair in a pig model of human lung diseases.

KeywordsLung mesenchymal stem cells Acute lung injury Stem cell Large animal model AbbreviationsBMBone marrow

CFSECarboxyfluorescein diacetate succinimidyl ester

CFU-FColony forming unit-fibroblast

DAPI4′,6-diamidino-2-phenylindole

DCDendritic cell

DMEMDulbecco’s modified Eagle’s medium

ELISAEnzyme-linked immunosorbent assay

FBSFetal bovine serum

IFAImmunofluorescence assay

IFNInterferon

ILInterleukin

L-MSCLung mesenchymal stem stromal cell

LPSLipopolysaccharide

MSCMesenchymal stem stromal cell

Oct4Octamer-binding transcription factor 4

ODOptical density

PBMCPeripheral blood mononuclear cell

PGE2Prostaglandin E2

PHAPhytohemagglutinin

SLASwine leucocyte antigen

ThT helper

TNFTumor necrosis factor

TregsT regulatory cells

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Author: Mahesh Khatri - Timothy D. O’Brien - Kuldeep S. Chattha - Linda J. Saif

Source: https://link.springer.com/



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