Human adipose-derived stromal cells in a clinically applicable injectable alginate hydrogel: Phenotypic and immunomodulatory evaluation
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Human adipose-derived stromal cells in a clinically applicable injectable alginate hydrogel : Phenotypic and immunomodulatory evaluation. / Larsen, Bjarke Follin; Juhl, Morten; Cohen, Smadar; Pedersen, Anders Elm; Gad, Monika; Kastrup, Jens; Ekblond, Annette.
I: Cytotherapy, Bind 17, Nr. 8, 08.2015, s. 1104-18.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Human adipose-derived stromal cells in a clinically applicable injectable alginate hydrogel
T2 - Phenotypic and immunomodulatory evaluation
AU - Larsen, Bjarke Follin
AU - Juhl, Morten
AU - Cohen, Smadar
AU - Pedersen, Anders Elm
AU - Gad, Monika
AU - Kastrup, Jens
AU - Ekblond, Annette
N1 - Copyright © 2015 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.
PY - 2015/8
Y1 - 2015/8
N2 - BACKGROUND AIMS: Clinical trials have documented beneficial effects of mesenchymal stromal cells from bone marrow and adipose tissue (ASCs) as treatment in patients with ischemic heart disease. However, retention of transplanted cells is poor. One potential way to increase cell retention is to inject the cells in an in situ cross-linked alginate hydrogel.METHODS: ASCs from abdominal human tissue were embedded in alginate hydrogel and alginate hydrogel modified with Arg-Gly-Asp motifs (RGD-alginate) and cultured for 1 week. Cell viability, phenotype, immunogenicity and paracrine activity were determined by confocal microscopy, dendritic cell co-culture, flow cytometry, reverse transcriptase quantitative polymerase chain reaction, Luminex multiplex, and lymphocyte proliferation experiments.RESULTS: ASCs performed equally well in alginate and RGD-alginate. After 1 week of alginate culture, cell viability was >93%. Mesenchymal markers CD90 and CD29 were reduced compared with International Society for Cellular Therapy criteria. Cells sedimented from the alginates during cultivation regained the typical level of these markers, and trilineage differentiation was performed by standard protocols. Hepatocyte growth factor mRNA was increased in ASCs cultivated in alginates compared with monolayer controls. Alginates and alginates containing ASCs did not induce dendritic cell maturation. ASCs in alginate responded like controls to interferon-gamma stimulation (licensing), and alginate culture increased the ability of ASCs to inhibit lymphocyte proliferation.DISCUSSION: ASCs remain viable in alginates; they transiently change phenotype in alginate hydrogel but regain the phenotype of monolayer controls upon release. Cells maintain their paracrine potential while in alginates; the combination of ASCs and alginate is non-immunogenic and, in fact, immunosuppressive.
AB - BACKGROUND AIMS: Clinical trials have documented beneficial effects of mesenchymal stromal cells from bone marrow and adipose tissue (ASCs) as treatment in patients with ischemic heart disease. However, retention of transplanted cells is poor. One potential way to increase cell retention is to inject the cells in an in situ cross-linked alginate hydrogel.METHODS: ASCs from abdominal human tissue were embedded in alginate hydrogel and alginate hydrogel modified with Arg-Gly-Asp motifs (RGD-alginate) and cultured for 1 week. Cell viability, phenotype, immunogenicity and paracrine activity were determined by confocal microscopy, dendritic cell co-culture, flow cytometry, reverse transcriptase quantitative polymerase chain reaction, Luminex multiplex, and lymphocyte proliferation experiments.RESULTS: ASCs performed equally well in alginate and RGD-alginate. After 1 week of alginate culture, cell viability was >93%. Mesenchymal markers CD90 and CD29 were reduced compared with International Society for Cellular Therapy criteria. Cells sedimented from the alginates during cultivation regained the typical level of these markers, and trilineage differentiation was performed by standard protocols. Hepatocyte growth factor mRNA was increased in ASCs cultivated in alginates compared with monolayer controls. Alginates and alginates containing ASCs did not induce dendritic cell maturation. ASCs in alginate responded like controls to interferon-gamma stimulation (licensing), and alginate culture increased the ability of ASCs to inhibit lymphocyte proliferation.DISCUSSION: ASCs remain viable in alginates; they transiently change phenotype in alginate hydrogel but regain the phenotype of monolayer controls upon release. Cells maintain their paracrine potential while in alginates; the combination of ASCs and alginate is non-immunogenic and, in fact, immunosuppressive.
KW - Adipocytes
KW - Adipose Tissue
KW - Adult
KW - Aged
KW - Aged, 80 and over
KW - Alginates
KW - Cell Differentiation
KW - Cell Proliferation
KW - Cell Survival
KW - Cells, Cultured
KW - Coculture Techniques
KW - Female
KW - Glucuronic Acid
KW - Hepatocyte Growth Factor
KW - Hexuronic Acids
KW - Humans
KW - Hydrogel
KW - Immunomodulation
KW - Interferon-gamma
KW - Male
KW - Mesenchymal Stem Cell Transplantation
KW - Mesenchymal Stromal Cells
KW - Middle Aged
KW - Oligopeptides
KW - RNA, Messenger
KW - Tissue Embedding
KW - Young Adult
U2 - 10.1016/j.jcyt.2015.04.008
DO - 10.1016/j.jcyt.2015.04.008
M3 - Journal article
C2 - 26031743
VL - 17
SP - 1104
EP - 1118
JO - Cytotherapy
JF - Cytotherapy
SN - 1465-3249
IS - 8
ER -
ID: 159742625