PMID- 37723658
OWN - NLM
STAT- MEDLINE
DCOM- 20231107
LR  - 20231114
IS  - 1552-4965 (Electronic)
IS  - 1549-3296 (Linking)
VI  - 112
IP  - 1
DP  - 2024 Jan
TI  - Heparin-collagen I bilayers stimulate FAK/ERK(1/2) signaling via alpha2beta1 integrin to 
      support the growth and anti-inflammatory potency of mesenchymal stromal cells.
PG  - 65-81
LID - 10.1002/jbm.a.37614 [doi]
AB  - Understanding mesenchymal stromal cells (MSCs) growth mechanisms in response to 
      surface chemistries is essential to optimize culture methods for high-quality and 
      robust cell yields in cell manufacturing applications. Heparin (HEP) and collagen 
      1 (COL) substrates have been reported to enhance cell adhesion, growth, 
      viability, and secretory potential in MSCs. However, the biomolecular mechanisms 
      underlying the benefits of combined HEP/COL substrates are unknown. This work 
      used HEP/COL bilayered surfaces to investigate the role of integrin-HEP 
      interactions in the advantages of MSC culture. The layer-by-layer approach (LbL) 
      was used to create HEP/COL bilayers, which were made up of stacks of 8 and 9 
      layers that combined HEP and COL in an alternate arrangement. Surface 
      spectroscopic investigations and laser scanning microscopy evaluations verified 
      the biochemical fingerprint of each component and a total stacked bilayer 
      thickness of roughly 150 nm. Cell growth and apoptosis in response to IC(50) and 
      IC(75) levels of BTT-3033 and Cilengitide, alpha2beta1 and alphavbeta3 integrin inhibitors 
      respectively, were evaluated on HEP/COL coated surfaces using two bone 
      marrow-derived MSC donors. While integrin activity did not affect cell growth 
      rates, it significantly affected cell adhesion and apoptosis on HEP/COL surfaces. 
      HEP-ending HEP/COL surfaces significantly increased FAK-ERK(1/2) phosphorylation and 
      endogenous cell COL deposition compared to COL, COL-ending HEP/COL and uncoated 
      surfaces. BTT-3033 but not Cilengitide treatment markedly affected FAK-ERK(1/2) 
      activity levels on HEP-ending HEP/COL surfaces supporting a major role for alpha2beta1 
      activity. BTT-3033 treatment on HEP-ending bilayers reduced MSC-mediated 
      macrophage inhibitory activity and altered the cytokine profile of co-cultures. 
      Overall, this study supports a novel role for HEP in regulating the survival and 
      potency of MSCs via enhancing the alpha2beta1-FAK-ERK(1/2) signaling mechanism.
CI  - (c) 2023 Wiley Periodicals LLC.
FAU - Cifuentes, Said J
AU  - Cifuentes SJ
AUID- ORCID: 0000-0002-3674-8382
AD  - Bioengineering Graduate Program, University of Puerto Rico Mayaguez, Mayaguez, 
      Puerto Rico, USA.
FAU - Domenech, Maribella
AU  - Domenech M
AUID- ORCID: 0000-0001-7061-8090
AD  - Bioengineering Graduate Program, University of Puerto Rico Mayaguez, Mayaguez, 
      Puerto Rico, USA.
AD  - Department of Chemical Engineering, University of Puerto Rico Mayaguez, Mayaguez, 
      Puerto Rico, USA.
LA  - eng
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20230918
PL  - United States
TA  - J Biomed Mater Res A
JT  - Journal of biomedical materials research. Part A
JID - 101234237
RN  - 0 (Integrins)
RN  - 9005-49-6 (Heparin)
RN  - 0 (Collagen Type I)
RN  - 0 (Integrin alpha2beta1)
SB  - IM
MH  - *Integrins/metabolism
MH  - Heparin/pharmacology
MH  - MAP Kinase Signaling System
MH  - Collagen Type I/metabolism
MH  - *Mesenchymal Stem Cells
MH  - Integrin alpha2beta1/metabolism
OTO - NOTNLM
OT  - collagen 1
OT  - heparin
OT  - human mesenchymal stromal cells
OT  - integrins
OT  - layer-by-layer
EDAT- 2023/09/19 06:42
MHDA- 2023/11/07 06:46
CRDT- 2023/09/19 00:53
PHST- 2023/08/25 00:00 [revised]
PHST- 2023/05/15 00:00 [received]
PHST- 2023/09/01 00:00 [accepted]
PHST- 2023/11/07 06:46 [medline]
PHST- 2023/09/19 06:42 [pubmed]
PHST- 2023/09/19 00:53 [entrez]
AID - 10.1002/jbm.a.37614 [doi]
PST - ppublish
SO  - J Biomed Mater Res A. 2024 Jan;112(1):65-81. doi: 10.1002/jbm.a.37614. Epub 2023 
      Sep 18.