Transcriptomics Comparison between Porcine Adipose and Bone Marrow Mesenchymal Stem Cells during In Vitro Osteogenic and Adipogenic Differentiation

Abstract

Bone-marrow mesenchymal stem cells (BMSC) are considered the gold standard for use in tissue regeneration among mesenchymal stem cells (MSC). The abundance and ease of harvest make the adipose-derived stem cells (ASC) an attractive alternative to BMSC. The aim of the present study was to compare the transcriptome of ASC and BMSC, respectively isolated from subcutaneous adipose tissue and femur of 3 adult pigs, during in vitro osteogenic and adipogenic differentiation for up to four weeks. At 0, 2, 7, and 21 days of differentiation RNA was extracted for microarray analysis. A False Discovery Rate ≤0.05 for overall interactions effect and P<0.001 between comparisons were used to determine differentially expressed genes (DEG). Ingenuity Pathway Analysis and DAVID performed the functional analysis of the DEG. Functional analysis of highest expressed genes in MSC and genes more expressed in MSC vs. fully differentiated tissues indicated low immunity and high angiogenic capacity. Only 64 genes were differentially expressed between ASC and BMSC before differentiation. The functional analysis uncovered a potential larger angiogenic, osteogenic, migration, and neurogenic capacity in BMSC and myogenic capacity in ASC. Less than 200 DEG were uncovered between ASC and BMSC during differentiation. Functional analysis also revealed an overall greater lipid metabolism in ASC, while BMSC had a greater cell growth and proliferation. The time course transcriptomic comparison between differentiation types uncovered <500 DEG necessary to determine cell fate. The functional analysis indicated that osteogenesis had a larger cell proliferation and cytoskeleton organization with a crucial role of G-proteins. Adipogenesis was driven by PPAR signaling and had greater angiogenesis, lipid metabolism, migration, and tumorigenesis capacity. Overall the data indicated that the transcriptome of the two MSC is relatively similar across the conditions studied. In addition, functional analysis data might indicate differences in therapeutic application.

Lineage depletion of stromal vascular fractions isolated from human adipose tissue: a novel approach towards cell enrichment technology

“…population might be of potential candidates for its use in tissue repair and regeneration. These results thus become highly imperative as it makes wider utilization of both depleted culture fractions for its implications in therapeutic applications unlike the existing uncertainties of SVF as indicated in the current literature (Kern et al 2006;Monaco et al 2012). The rationale behind the applicability could be unravelled by the analysis of its marker expression profiles obtained from cultured lin-and lin?…”

Invited review: Pre- and postnatal adipose tissue development in farm animals: from stem cells to adipocyte physiology

“…Among other MSCs, the investigation of ADSCs is quite recent but is of considerable interest because of their quantity and accessibility compared with bone marrow cells. They share many biological similarities with bone marrow MSCs but exhibit some specificity as shown in pigs (Monaco et al, 2012). The characterization of ADSCs is based on the expression of several clusters of differentiation (CD) markers (Figure 2) using flow cytometry and fluorescence-activated cell sorting (FACS).…”

“…Ding et al, 1999;Kim et al, 2000;McNeel et al, 2000). The transcriptional program is also largely similar for the white and brown adipocytes (Koppen and Kalkhoven, 2010), and involves many genes that are sequentially under-or over-expressed as revealed by expression studies including high-throughtput omics technologies (see for pigs Monaco et al, 2012; and for cattle, Taga et al, 2012a). A concerted cooperation of numerous transcription factors together with their coactivators and corepressors is also needed.…”

Estudo comparativo da diferenciação osteogênica das células tronco mesenquimais da medula óssea e do tecido adiposo de cães adultos

“…Muitos estudos já foram realizados em humanos e ratos mas, pouco se sabe sobre o potencial osteogênico dessas células em outras espé-cies como o cão. Alguns pesquisadores demonstram que as CTM oriundas da medula óssea (CTM-MO) apresentam maior potencial osteogênico que as CTM do tecido adiposo (CTM-AD) , Monaco et al 2012, outros indicam maior potencial osteogênico nas CTM-AD (Lin et al 2009, Chung et al 2012) e existem aqueles que mostram potencial osteogênico semelhante entre os dois tipos celulares (Spencer et al 2012, Ranera et al 2012. Em cães, os estudos comparativos entre CTM-MO e CTM-AD são escassos.…”