TY - JOUR
T1 - Evaluation of the effect of donor weight on adipose stromal/stem cell characteristics by using weight-discordant monozygotic twin pairs
AU - Juntunen, Miia
AU - Heinonen, Sini
AU - Huhtala, Heini
AU - Rissanen, Aila
AU - Kaprio, Jaakko
AU - Kuismanen, Kirsi
AU - Pietiläinen, Kirsi H.
AU - Miettinen, Susanna
AU - Patrikoski, Mimmi
N1 - Funding Information:
The authors thank Ms. Anna-Maija Honkala and Ms. Sari Kalliokoski for excellent technical assistance. We thank the Tampere Imaging Facility, Outi Paloheimo, Juha Heikkil? and Tarja Toimela for technical assistance in the angiogenesis potential assays. We thank Antti Aula for technical assistance in the cell irradiation.
Funding Information:
This work was supported by Business Finland and the Academy of Finland (Grant Nos. 326588 to SM and 311084 to MP), the Competitive State Research Financing of the Expert Responsibility area of Tampere University Hospital, the Finnish Cultural Foundation (Grant No. 00190409 to MJ) and the Tampere University Graduate School for Medicine and Life Sciences (MJ). SH was supported by Helsinki University Hospital funds, the Finnish Diabetes Research Foundation, the Orion Foundation, the Paulo Foundation, the Finnish Medical Foundation and the Maud Kuistila Foundation. KHP was supported by the Academy of Finland (Grant Nos. 272376, 314383, and 266286), the Finnish Medical Foundation, the Gyllenberg Foundation, the Finnish Diabetes Research Foundation, the Sigrid Juselius Foundation, the Novo Nordisk Foundation (NNF17OC0027232 and NNF10OC1013354), the University of Helsinki and the Government Research Funds through Helsinki University Hospital. JK was supported by the Academy of Finland Centre of Excellence in Complex Disease Genetics (Grant 312073).
PY - 2021/9
Y1 - 2021/9
N2 - Background: Adipose 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. Methods: ASCs 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. Results: ASCs 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. Conclusions: Our 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.
AB - Background: Adipose 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. Methods: ASCs 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. Results: ASCs 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. Conclusions: Our 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.
KW - Adipose stem cells
KW - Cell surface markers
KW - Differentiation
KW - Immunogenicity
KW - Immunosuppression
KW - Proliferation
U2 - 10.1186/s13287-021-02587-0
DO - 10.1186/s13287-021-02587-0
M3 - Article
AN - SCOPUS:85115704241
SN - 1757-6512
VL - 12
JO - Stem Cell Research and Therapy
JF - Stem Cell Research and Therapy
M1 - 516
ER -