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Nanoparticles from Equine Fetal Bone Marrow-Derived Cells Enhance the Survival of Injured Chondrocytes.

ABSTRACT: Recent studies have shown that mesenchymal stem cells (MSCs) can play a restorative role against degenerative joint diseases in horses. The purpose of this study was to investigate whether fetal bone marrow-derived cells (BMC)-derived nanoparticles (BMC-NPs) can stimulate the survival of equine chondrocytes. Equine fetal BMCs were isolated and characterized, and the role of BMC-NPs s in equine chondrocytes undergoing inflammatory cell death was examined. BMCs have several characteristics, such as the potential to differentiate into chondrocytes and osteocytes. Additionally, BMCs expressed immunoregulatory genes in response to treatment with tumor necrosis factor-alpha (TNF-?) and Interleukin 1 beta (IL-1?). We found that BMC-NPs were taken up by equine chondrocytes. Functionally, BMC-NPs promoted the growth of chondrocytes, and reduced apoptosis induced by inflammatory cytokines. Furthermore, we observed that BMC-NPs upregulated the phosphorylation of protein kinase B (Akt) in the presence of IL-1?, and reduced the phosphorylation of TNF-?-induced activation of extracellular signal-regulated kinase 1/2 (ERK1/2) in the chondrocytes. Cumulatively, our study demonstrated that equine fetal BMC-NPs have the potential to stimulate the survival of chondrocytes damaged by inflammatory cytokines. Thus, BMC-NPs may become an alternative cell-free allogenic therapeutic for degenerative joint diseases in horses.

SUBMITTER: Kim KH

PROVIDER: S-EPMC7598183 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Nanoparticles from Equine Fetal Bone Marrow-Derived Cells Enhance the Survival of Injured Chondrocytes.

Kim Ki Hoon KH Park Tae Sub TS Cho Byung-Wook BW Kim Tae Min TM

Animals : an open access journal from MDPI 20200923 10

Recent studies have shown that mesenchymal stem cells (MSCs) can play a restorative role against degenerative joint diseases in horses. The purpose of this study was to investigate whether fetal bone marrow-derived cells (BMC)-derived nanoparticles (BMC-NPs) can stimulate the survival of equine chondrocytes. Equine fetal BMCs were isolated and characterized, and the role of BMC-NPs s in equine chondrocytes undergoing inflammatory cell death was examined. BMCs have several characteristics, such a ...[more]

PMID: 32977476

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Project description:Background - The mesenchymal stem cells (MSCs) have a unique self-renewal and developmental potential resulting from their multipotency – the ability to differentiate into particular cell types. It has been confirmed that MSCs have a huge potential and outstanding therapeutic effects in variety of clinical treatments due to the their abilities to differentiate towards ectodermal, endodermal, and mesodermal cell lines. Objectives - the project aims to identify changes in MSCs transcriptome profile during the process of losing multipotency and acquiring the ability to differentiate cells into adipocytes (ADM) and chondrocytes (CDM) equine cell lines. Methods - Bone marrow-derived MSCs were differentiated towards adipocytes and chondrocytes using different procedures. The specificity of obtained cell lines was checked using qPCR, cytometry, and staining approaches. The transcriptome analysis was performed using NGS transcript sequencing on the Illumina HiSeq 3000 platform. Results - The differential expression analysis allowed us to identify the 2325 DEGs between MSC and ADM groups, while 803 DEGs were detected between MCS and CDM cell lines. According to the comparison of both DEG sets the expression of 320 genes was significantly modified despite the direction of differentiation. The direct related to the transformation of MSCs into adipocytes seems to be fat cell differentiation represented by 47 DEGs and included additional GOs as regulation of fat cell differentiation, regulation of cell differentiation, brown fat cell differentiation, and adipocyte fat development. The results indicated the top DEGs involved in differentiation into adipocytes and previously established as related to adipogenesis: down-regulated - MEOX1, CYYR1, and up-regulated – CYP24A1; LEP; TBX5; FABP4 and GPER1. The obtained data indicated molecular mechanism altered during equine cell remodelling towards chondrocyte differentiation. One of identified GOs was ossification process represented by 35 DEGs with the highest up regulation of two genes was observed - IHH (6.46) and PHOSPHO1 (5.46) involved in chondrocyte proliferation and matrix mineralisation; respectively. The highest down regulation was detected for BMPR1B gene, critical for bone and cartilage formation (-5.98) and together with BMP2 and BMP4 (2.26 and 2.48; respectively) triggered BMP signaling. Conclusions - The obtained picture of transcriptome differences between primary donor cells and reprogrammed cell lines revealed a range of transcripts important for molecular alterations resulting from substantial phenotypic change of reprogramed cells under special ex-vivo procedures. The study showed the effects of the radical change of cell fate decisions on the molecular level and reinforced further work on efficient procedures to produce MSC-derived reprogrammed cells that have the potential for regenerative medicine of hard connective tissue in horses.

Project description:BackgroundCo-transplantation of bone marrow cells (BMCs) and mesenchymal stem cells (MSCs) is used as a strategy to improve the outcomes of bone marrow transplantation. Tonsil-derived MSCs (TMSCs) are a promising source of MSCs for co-transplantation. Previous studies have shown that TMSCs or conditioned media from TMSCs (TMSC-CM) enhance BMC engraftment. However, the factors in TMSCs that promote better engraftment have not yet been identified.MethodsMice were subjected to a myeloablative regimen of busulfan and cyclophosphamide, and the mRNA expression in the bone marrow was analyzed using an extracellular matrix (ECM) and adhesion molecule-targeted polymerase chain reaction (PCR) array. Nano-liquid chromatography with tandem mass spectrometry, real-time quantitative PCR, western blots, and enzyme-linked immunosorbent assays were used to compare the expression levels of metalloproteinase 3 (MMP3) in MSCs derived from various tissues, including the tonsils, bone marrow, adipose tissue, and umbilical cord. Recipient mice were conditioned with busulfan and cyclophosphamide, and BMCs, either as a sole population or with control or MMP3-knockdown TMSCs, were co-transplanted into these mice. The effects of TMSC-expressed MMP3 were investigated. Additionally, Enzchek collagenase and Transwell migration assays were used to confirm that the collagenase activity of TMSC-expressed MMP3 enhanced BMC migration.ResultsMice subjected to the myeloablative regimen exhibited increased mRNA expression of collagen type IV alpha 1/2 (Col4a1 and Col4a2). Among the various extracellular matrix-modulating proteins secreted by TMSCs, MMP3 was expressed at higher levels in TMSCs than in other MSCs. Mice co-transplanted with BMCs and control TMSCs exhibited a higher survival rate, weight recovery, and bone marrow cellularity compared with mice co-transplanted with BMCs and MMP3-knockdown TMSCs. Control TMSC-CM possessed higher collagenase activity against collagen IV than MMP3-knockdown TMSC-CM. TMSC-CM also accelerated BMC migration by degrading collagen IV in vitro.ConclusionsCollectively, these results indicate that TMSCs enhance BMC engraftment by the secretion of MMP3 for the modulation of the bone marrow extracellular matrix.

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Dataset Information

Nanoparticles from Equine Fetal Bone Marrow-Derived Cells Enhance the Survival of Injured Chondrocytes.

Publications

Nanoparticles from Equine Fetal Bone Marrow-Derived Cells Enhance the Survival of Injured Chondrocytes.

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