Influence of BMI on level of circulating progenitor cells

Abstract

Obesity complicates a number of diseases through mechanisms that are poorly defined. Mobilization and recruitment of progenitor cells to pathological sites is an important factor in disease progression. Here, we analyzed the influence of obesity on the systemic circulation of CD34(+) cell populations and correlated frequencies of cells displaying previously established cell marker signatures with the BMI. Comparative analysis of peripheral blood mononuclear cells (PBMC) from 12 nonobese (BMI <30 kg/m(2)) and 14 obese (BMI >30 kg/m(2)) disease-free donors by flow cytometry revealed that obesity is associated with a fivefold increased frequency of circulating progenitor cells (CPC), a population consisting of hematopoietic and endothelial precursors. Our data also indicate that obesity is associated with increased frequency of circulating mesenchymal stromal progenitor cells (MSC). In contrast, the frequencies of mature endothelial cells (EC) and CD34-bright leukocytes are unaffected by obesity. Combined, our results indicate that obesity promotes mobilization of progenitor cells, which may have clinical relevance.

Figure 1

Enumeration of cell populations in peripheral blood. (a) FSC-H/FSC-A graph: gating on single cells; exclusion of cell clumps, erythrocytes, platelets, endothelial cells (EC) microparticles, and debris. SSC-A/FSC-A graph: gating on mononuclear cells. 7-AAD/SSC-A graph: gating on viable peripheral blood mononuclear cells (PBMCs). The gating diagram on the right indicates that circulating progenitor cells (CPC), CD34bright (CD34b) leukocytes (LC), EC, and CD34bCD45⁻CD31⁻ cells are enumerated as sub-populations of viable PBMC. (b) Enumeration of circulating cells by flow cytometry: representative data from a lean (upper panel) and an obese (lower panel) donor. The cutoffs for CD31, CD34, and CD45 bright, dim, and negative (−) cells, as indicated, are based on the position of previously characterized (11) CPC and EC populations; CD34bCD45⁻CD31⁻ cells and CD34b LC are identified relative to EC and CPC localization on the plots. The plots on the right include only cells gated as CPC and CD34bCD45⁻CD31⁻ cells in the middle panels. (c) Phase contrast micrographs of cell cultures (1 week) derived from the corresponding cell populations sorted in b. Note the expected morphology of HPC, EC, and monocytoid CD34b leukocytes attached to plastic. (d) A clone of mesenchymal stromal cells (MSC) derived from PBMC of a BMI >30 subject after 3 weeks of culture. Bar = 50 µM. (e) Frequencies of cell populations in PBMC as a function of BMI. Flow cytometric enumeration of CPC, EC, CD34b LC, and CD34bCD45⁻CD31⁻ cells was performed for disease-free donors with BMI <30 (N = 12), and BMI >30 (N = 14). Shown are mean % of viable PBMC ± s.e. of the mean. *P < 0.01 (Mann–Whitney U-test).