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

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/m(2)) 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.Peer reviewe

Kuinka hoidan ympärileikattua naista?

Maahanmuuton lisääntyessä terveydenhuollossa kohdataan yhä useammin potilaana naisia, jotka on ympärileikattu ennen tuloa Suomeen. Terveydenhuoltohenkilöstön on tärkeää osata ottaa ympärileikkaukseen liittyvät ongelmat puheeksi erityisesti naisten ollessa raskaana. Avausleikkausta tulisi tarjota oireisille naisille. Se voidaan tehdä raskauden tai synnytyksen aikana tai mieluiten jo sukupuolielämän alkaessa. Vastasyntyneen lapsen vanhemmille on tärkeää kertoa, että tyttöjen ympärileikkaus on Suomessa kielletty.Peer reviewe

Mereiset avainluontotyypit ympäristöluvituksessa

Merialueiden käyttö kasvaa maailmanlaajuisesti. Kun yhä suurempaa osaa meri- ja ranta-alueista hyödynnetään taloudellisesti, lisääntyvät myös meriympäristöön kohdistuvat paineet, minkä seurauksena meriekosysteemin tila heikkenee. Meriekosysteemin toiminta ja meren meille tarjoamien ekosysteemipalveluiden määrä ja laatu voivat kasvavien paineiden myötä heikentyä. Tässä selvityksessä arvioidaan, miten mereiset luontoarvot on huomioitu Suomen rannikolla ja merialueilla tehdyssä ympäristölupaharkinnassa. Selvityksessä käytiin läpi ympäristö- ja vesilupia Suomen merialueella vuosilta 2014–2019, arvioitiin niihin sisällytettyjä meriympäristön rakennepiirteitä ja käytettyjä aineistoja, sekä vertailtiin luvituksen lopputuloksia. Tämän lisäksi selvitykseen koottiin mereisten avainluontotyyppien suojelua parantavia suosituksia. Aluehallintoviraston hallinnoimasta avoimesta Lupa-tietopalvelusta poimittiin yhteensä 77 hanketta liittyen ja/tai vaikuttaen mereen. Lupia anottiin eniten vuosina 2015 ja 2018. Lähes kaikki hakemukset koskivat uusia meri- ja rannikkoalueen käyttöön liittyviä hankkeita ja suurin osa kaikista hakemuksista myös hyväksyttiin. Lupahakemusten määrässä oli eroja myös merialueittain. Lupaprosesseihin liittyviä ympäristövaikutusten arvioita (YVA) edellytettiin harvoin; lähtökohtaisesti YVA:a edellytettiin hankkeilta, joilla arvioitiin mahdollisesti olevan merkittäviä vaikutuksia meriympäristölle. Hankkeissa arvioituja meriympäristöön liittyviä muuttujia arvioitiin vaihtelevasti; vesipuitedirektiiviin suoraan liittyviä vesimuodostumien ekologiseen laatuun liittyviä tekijöitä ja hankkeen vaikutuksia virkistyskäyttöön arvioitiin yleisimmin. Hankkeiden vaikutuksista meriympäristöön tehtiin asiantuntija-arvio, jossa ympäristöön kohdistuvat haittavaikutukset luokiteltiin kolmeen eri luokkaan. Ihmistoiminnan kumulatiivisia vaikutuksia oli arvioitu hyvin harvassa lupahakemuksessa. Kalastoon kohdistuvia taloudellisia kompensaatiotoimia edellytettiin 11 luparatkaisussa, mutta ekologisia tai ravinnekompensaatioita ei luparatkaisuissa määrätty. Koostettuun aineistoon perustuen, meriekosysteemin rakenteen ja toiminnan kannalta keskeiset avainluontotyypit on huomioitu Suomen rannikolla tehdyissä luvituspäätöksissä puutteellisesti. Raportin suositukset liittyvät tarpeeseen tarkentaa meriluonnon monimuotoisuutteen liittyvää sääntelyä ja luvituskäytäntöjä, aineistojen saatavuuden parantamiseen ja yhteisvaikutusten huomiointiin, jotta meri- ja rannikkoalueiden avainluontotyyppien suojelua voi parantaa

Angiogenic Potential of Human Adipose-Derived Mesenchymal Stromal Cells in Nanofibrillated Cellulose Hydrogel

Adipose-derived mesenchymal stromal cells (ASCs) hold great potential for cellular therapies by having immunomodulatory behavior and tissue regenerative properties. Due to the capability of ASCs to differentiate into endothelial cells (ECs) and other angiogenic cell types, such as pericytes, ASCs are a highly valuable source for stimulating angiogenesis. However, cellular therapies in tissue engineering have faced challenges in poor survival of the cells after transplantation, which is why a protective biomaterial scaffold is required. In this work, we studied the potential of nanofibrillated cellulose (NFC) hydrogel to be utilized as a suitable matrix for three-dimensional (3D) cell culturing of human-derived ASCs (hASCs) and studied their angiogenic properties and differentiation potential in ECs and pericytes. In addition, we tested the effect of hASC-conditioned medium and stimulation with angiopoietin-1 (Ang-1) on human umbilical vein endothelial cells (HUVECs) to induce blood vessel-type tube formation in NFC hydrogel. The hASCs were successfully 3D cell cultured in NFC hydrogel as they formed spheroids and had high cell viability with angiogenic features. Most importantly, they showed angiogenic potential by having pericyte-like characteristics when differentiated in EC medium, and their conditioned medium improved HUVEC viability and tube formation, which recalls the active paracrine properties. This study recommends NFC hydrogel for future use as an animal-free biomaterial scaffold for hASCs in therapeutic angiogenesis and other cell therapy purposes

Growth Response and Differentiation of Bone Marrow-Derived Mesenchymal Stem/Stromal Cells in the Presence of Novel Multiple Myeloma Drug Melflufen

Mesenchymal stem/stromal cells (MSCs) are self-renewing and multipotent progenitors, which constitute the main cellular compartment of the bone marrow stroma. Because MSCs have an important role in the pathogenesis of multiple myeloma, it is essential to know if novel drugs target MSCs. Melflufen is a novel anticancer peptide–drug conjugate compound for patients with relapsed refractory multiple myeloma. Here, we studied the cytotoxicity of melflufen, melphalan and doxorubicin in healthy human bone marrow-derived MSCs (BMSCs) and how these drugs affect BMSC proliferation. We established co-cultures of BMSCs with MM.1S myeloma cells to see if BMSCs increase or decrease the cytotoxicity of melflufen, melphalan, bortezomib and doxorubicin. We evaluated how the drugs affect BMSC differentiation into adipocytes and osteoblasts and the BMSC-supported formation of vascular networks. Our results showed that BMSCs were more sensitive to melflufen than to melphalan. The cytotoxicity of melflufen in myeloma cells was not affected by the co-culture with BMSCs, as was the case for melphalan, bortezomib and doxorubicin. Adipogenesis, osteogenesis and BMSC-mediated angiogenesis were all affected by melflufen. Melphalan and doxorubicin affected BMSC differentiation in similar ways. The effects on adipogenesis and osteogenesis were not solely because of effects on proliferation, seen from the differential expression of differentiation markers normalized by cell number. Overall, our results indicate that melflufen has a significant impact on BMSCs, which could possibly affect therapy outcome

Growth Response and Differentiation of Bone Marrow-Derived Mesenchymal Stem/Stromal Cells in the Presence of Novel Multiple Myeloma Drug Melflufen

Mesenchymal stem/stromal cells (MSCs) are self-renewing and multipotent progenitors, which constitute the main cellular compartment of the bone marrow stroma. Because MSCs have an important role in the pathogenesis of multiple myeloma, it is essential to know if novel drugs target MSCs. Melflufen is a novel anticancer peptide–drug conjugate compound for patients with relapsed refractory multiple myeloma. Here, we studied the cytotoxicity of melflufen, melphalan and doxorubicin in healthy human bone marrow-derived MSCs (BMSCs) and how these drugs affect BMSC proliferation. We established co-cultures of BMSCs with MM.1S myeloma cells to see if BMSCs increase or decrease the cytotoxicity of melflufen, melphalan, bortezomib and doxorubicin. We evaluated how the drugs affect BMSC differentiation into adipocytes and osteoblasts and the BMSC-supported formation of vascular networks. Our results showed that BMSCs were more sensitive to melflufen than to melphalan. The cytotoxicity of melflufen in myeloma cells was not affected by the co-culture with BMSCs, as was the case for melphalan, bortezomib and doxorubicin. Adipogenesis, osteogenesis and BMSC-mediated angiogenesis were all affected by melflufen. Melphalan and doxorubicin affected BMSC differentiation in similar ways. The effects on adipogenesis and osteogenesis were not solely because of effects on proliferation, seen from the differential expression of differentiation markers normalized by cell number. Overall, our results indicate that melflufen has a significant impact on BMSCs, which could possibly affect therapy outcome

Growth Response and Differentiation of Bone Marrow-Derived Mesenchymal Stem/Stromal Cells in the Presence of Novel Multiple Myeloma Drug Melflufen

Mesenchymal stem/stromal cells (MSCs) are self-renewing and multipotent progenitors, which constitute the main cellular compartment of the bone marrow stroma. Because MSCs have an important role in the pathogenesis of multiple myeloma, it is essential to know if novel drugs target MSCs. Melflufen is a novel anticancer peptide-drug conjugate compound for patients with relapsed refractory multiple myeloma. Here, we studied the cytotoxicity of melflufen, melphalan and doxorubicin in healthy human bone marrow-derived MSCs (BMSCs) and how these drugs affect BMSC proliferation. We established co-cultures of BMSCs with MM.1S myeloma cells to see if BMSCs increase or decrease the cytotoxicity of melflufen, melphalan, bortezomib and doxorubicin. We evaluated how the drugs affect BMSC differentiation into adipocytes and osteoblasts and the BMSC-supported formation of vascular networks. Our results showed that BMSCs were more sensitive to melflufen than to melphalan. The cytotoxicity of melflufen in myeloma cells was not affected by the co-culture with BMSCs, as was the case for melphalan, bortezomib and doxorubicin. Adipogenesis, osteogenesis and BMSC-mediated angiogenesis were all affected by melflufen. Melphalan and doxorubicin affected BMSC differentiation in similar ways. The effects on adipogenesis and osteogenesis were not solely because of effects on proliferation, seen from the differential expression of differentiation markers normalized by cell number. Overall, our results indicate that melflufen has a significant impact on BMSCs, which could possibly affect therapy outcome.Peer reviewe

Angiogenic Potential of Human Adipose-Derived Mesenchymal Stromal Cells in Nanofibrillated Cellulose Hydrogel

Adipose-derived mesenchymal stromal cells (ASCs) hold great potential for cellular therapies by having immunomodulatory behavior and tissue regenerative properties. Due to the capability of ASCs to differentiate into endothelial cells (ECs) and other angiogenic cell types, such as pericytes, ASCs are a highly valuable source for stimulating angiogenesis. However, cellular therapies in tissue engineering have faced challenges in poor survival of the cells after transplantation, which is why a protective biomaterial scaffold is required. In this work, we studied the potential of nanofibrillated cellulose (NFC) hydrogel to be utilized as a suitable matrix for three-dimensional (3D) cell culturing of human-derived ASCs (hASCs) and studied their angiogenic properties and differentiation potential in ECs and pericytes. In addition, we tested the effect of hASC-conditioned medium and stimulation with angiopoietin-1 (Ang-1) on human umbilical vein endothelial cells (HUVECs) to induce blood vessel-type tube formation in NFC hydrogel. The hASCs were successfully 3D cell cultured in NFC hydrogel as they formed spheroids and had high cell viability with angiogenic features. Most importantly, they showed angiogenic potential by having pericyte-like characteristics when differentiated in EC medium, and their conditioned medium improved HUVEC viability and tube formation, which recalls the active paracrine properties. This study recommends NFC hydrogel for future use as an animal-free biomaterial scaffold for hASCs in therapeutic angiogenesis and other cell therapy purposes.publishedVersionPeer reviewe

Endometrioosin diagnostiikka ja hoito TAYS:ssa vuosina 1988-1989.

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