BACKGROUND: Fat is stored in adipose tissue. In obesity, differentiation of preadipocytes to new adipocytes (fat cells) is required for energy storage. Otherwise fat accumulation in non-adipocytes contributes to fatty liver and diabetes. Our goal was to assess subject characteristics associated with poor in-vitro differentiation capacity of preadipocytes from omental (OM) and abdominal subcutaneous (SC) fat. APPROACH: A convenience sample of, 4 males and 20 females, age 39±2 (range 20-56) years, BMI 42 ± 2 (23-63) kg/m2 (i.e. from lean to obese), 7 Caucasian, 8 Hispanic, 1 other and 8 African Americans) undergoing elective surgery was studied. Fat samples collected during surgery were used for histology and preadipocyte isolation. Fat cell diameters and their distribution (normal or bimodal) were analyzed from histology. Preadipocyte differentiation capacity was measured in vitro. RESULTS: In the OM depot, no effect of ethnicity, sex or HbA1c was found. Unexpectedly, subjects with preadipocytes with poor differentiation capacity tended to be younger (poor differentiation group 36 ± 2 years versus high 43 ± 3 years, p=0.09) and to have lower fasting glucose (poor 97 ± 3.65 mg/dl versus high 111 ± 7.08 mg/dl, p=0.06). In SC, no differences were noted. Fat cell size was not associated with differentiation capacity in either depot. Bimodal distribution, which may show formation of new adipocytes, was seen mostly in Caucasian subjects (5 out of 7) compared to Hispanic (3 out of 8) and African Americans (2 out of 8). CONCLUSION: It is important to investigate the associations between age/ethnicity and OM preadipocyte differentiation/cell distribution in adequately powered cross-sectional studies.

Bone transplantation is regarded as the preferred therapy to treat a variety of bone defects. Autologous bone tissue is often lacking at the source, and the mesenchymal stem cells (MSCs) responsible for bone repair mechanisms are extracted by invasive procedures. This study explores the potential of autologous mesenchymal stem cells derived from the hair follicle outer root sheath (MSCORS). We demonstrated that MSCORS have a remarkable capacity to differentiate in vitro towards the osteogenic lineage. Indeed, when combined with a novel gelatin-based hydrogel called Osteogel, they provided additional osteoinductive cues in vitro that may pave the way for future application in bone regeneration. MSCORS were also compared to MSCs from adipose tissue (ADMSC) and bone marrow (BMMSC) in a 3D Osteogel model. We analyzed gel plasticity, cell phenotype, cell viability, and differentiation capacity towards the osteogenic lineage by measuring alkaline phosphatase (ALP) activity, calcium deposition, and specific gene expression. The novel injectable hydrogel filled an irregularly shaped lesion in a porcine wound model displaying high plasticity. MSCORS in Osteogel showed a higher osteo-commitment in terms of calcium deposition and expression dynamics of OCN, BMP2, and PPARG when compared to ADMSC and BMMSC, whilst displaying comparable cell viability and ALP activity. In conclusion, autologous MSCORS combined with our novel gelatin-based hydrogel displayed a high capacity for differentiation towards the osteogenic lineage and are acquired by non-invasive procedures, therefore qualifying as a suitable and expandable novel approach in the field of bone regeneration therapy