Evaluation of the effect of donor weight on adipose stromal/stem cell characteristics by using weight-discordant monozygotic twin pairs

Miia Juntunen,Kirsi Kuismanen,Mimmi Patrikoski,Jaakko Kaprio,Sini Heinonen,Aila Rissanen,Kirsi H Pietiläinen,Susanna Miettinen,Heini Huhtala

doi:10.1186/s13287-021-02587-0

Abstract

BackgroundAdipose stromal/stem cells (ASCs) are promising candidates for future clinical applications. ASCs have regenerative capacity, low immunogenicity, and immunomodulatory ability. The success of future cell-based therapies depends on the appropriate selection of donors. Several factors, including age, sex, and body mass index (BMI), may influence ASC characteristics. Our aim was to investigate the effect of acquired weight on ASC characteristics under the same genetic background using ASCs derived from monozygotic (MZ) twin pairs.MethodsASCs were isolated from subcutaneous adipose tissue from five weight-discordant (WD, within-pair difference in BMI > 3 kg/m2) MZ twin pairs, with measured BMI and metabolic status. The ASC immunophenotype, proliferation and osteogenic and adipogenic differentiation capacity were studied. ASC immunogenicity, immunosuppression capacity and the expression of inflammation markers were investigated. ASC angiogenic potential was assessed in cocultures with endothelial cells.ResultsASCs showed low immunogenicity, proliferation, and osteogenic differentiation capacity independent of weight among all donors. ASCs showed a mesenchymal stem cell-like immunophenotype; however, the expression of CD146 was significantly higher in leaner WD twins than in heavier cotwins. ASCs from heavier twins from WD pairs showed significantly greater adipogenic differentiation capacity and higher expression of TNF and lower angiogenic potential compared with their leaner cotwins. ASCs showed immunosuppressive capacity in direct cocultures; however, heavier WD twins showed stronger immunosuppressive capacity than leaner cotwins.ConclusionsOur genetically matched data suggest that a higher weight of the donor may have some effect on ASC characteristics, especially on angiogenic and adipogenic potential, which should be considered when ASCs are used clinically.

Highlights

Adipose stromal/stem cells (ASCs) are multipotent mesenchymal stromal/stem cells (MSCs) that represent a promising tool for tissue regeneration applications as well as for cell-based treatment of inflammatory and Juntunen et al Stem Cell Res Ther (2021) 12:516 autoimmune conditions [1]
In four out of five WD twin pairs, heavier cotwins showed elevated levels of Lowdensity lipoprotein (LDL), high-sensitivity C reactive protein (hs-CRP), and leptin and impaired insulin sensitivity measured as Insulin resistance index (HOMA-IR) compared with leaner cotwins
The results of surface marker expression of ASCs isolated from each MZ twin donor are shown in Additional file 1: Table 5 and morphology in Additional file 7: Figure 6

Summary

Introduction

Adipose stromal/stem cells (ASCs) are multipotent mesenchymal stromal/stem cells (MSCs) that represent a promising tool for tissue regeneration applications as well as for cell-based treatment of inflammatory and Juntunen et al Stem Cell Res Ther (2021) 12:516 autoimmune conditions [1]. Several factors of the donor, such as age [3,4,5] and sex [6], have been suggested to affect ASC characteristics. The osteogenic differentiation [4,5,6] and proliferation [7] capacity of ASCs have been shown to differ according to donor properties. Adipose stromal/stem cells (ASCs) are promising candidates for future clinical applications. The success of future cell-based therapies depends on the appropriate selection of donors. Several factors, including age, sex, and body mass index (BMI), may influence ASC characteristics. Our aim was to investigate the effect of acquired weight on ASC characteristics under the same genetic background using ASCs derived from monozygotic (MZ) twin pairs

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