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Calcification and cellularity in human aortic heart valve tissue determine the differentiation of bone-marrow-derived cells

Leskela, Hannu-Ville ; Satta, Jari ; Oiva, Jani ; Eriksen, Heidi ; Juha, Risteli ; Korkiamaki, Paula ; Ivaska, Kaisa LU ; Soini, Ylermi and Lehenkari, Petri (2006) In Journal of Molecular and Cellular Cardiology 41(4). p.642-649
Abstract
Human bone-marrow-derived mesenchymal stem cells (MSC) are responsible the remodeling of human tissue. However, damaged aortic valves are lack the ability to regenerate which is an active cell-mediated process. Diseased aortic valve remodeling has similarities even to bone formation. In this study, the prerequisites for cultured MSCs to undergo osteoblastic differentiation on aortic valves were explored. An ex vivo model using a human aortic valve microenvironment was developed. The expression of type I procollagen, alkaline phosphatase activity, osteocalcin secretion and osteocalcin immunostaining were studied to evaluate the induction of osteogenesis of the MSCs on noncalcified and calcified human aortic valves. Aortic valves were... (More)
Human bone-marrow-derived mesenchymal stem cells (MSC) are responsible the remodeling of human tissue. However, damaged aortic valves are lack the ability to regenerate which is an active cell-mediated process. Diseased aortic valve remodeling has similarities even to bone formation. In this study, the prerequisites for cultured MSCs to undergo osteoblastic differentiation on aortic valves were explored. An ex vivo model using a human aortic valve microenvironment was developed. The expression of type I procollagen, alkaline phosphatase activity, osteocalcin secretion and osteocalcin immunostaining were studied to evaluate the induction of osteogenesis of the MSCs on noncalcified and calcified human aortic valves. Aortic valves were exposed to freeze-thaw injury to devitalize valves in order to separately study the role of valve matrix vs. endothelial cells in the explants. Thus, valves were assigned to 1 of 4 treatment groups: noncalcified uninjured valves, calcified uninjured valves, noncalcified injured and calcified injured. Finally, valves were decalcified to separately explore the effect of a calcified matrix on the osteogenesis. In this co-culture system, the noncalcified uninjured valves inhibited osteogenesis of MSCs, whereas the calcified valves promoted differentiation towards osteoblastic lineage. Devitalization of the valve matrix inflicted a significant increase in the osteogenesis of co-cultured MSCs. Calcified matrix in the valves seemed to have a role in the spontaneous osteogenesis of the MSCs. This spontaneous matrix induced differentiation of MSCs into osteoblast lineage could not be inhibited by pravastatin, indomethacin or tetracycline. In conclusion, these results suggest that interactions between MSCs and aortic valve matrix components and cells modulate MSC phenotype in this environment. Further studies are required to characterize this interesting phenomenon in greater detail. (Less)
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author
; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Aortic valves, Mesenchymal stem cells, Differentiation, Co-culture, Osteogenesis
in
Journal of Molecular and Cellular Cardiology
volume
41
issue
4
pages
642 - 649
publisher
Elsevier
external identifiers
  • pmid:16938307
  • scopus:33748573243
ISSN
1095-8584
DOI
10.1016/j.yjmcc.2006.07.014
language
English
LU publication?
yes
id
90d90826-4083-4249-ba36-36a55d78119d (old id 1136575)
date added to LUP
2016-04-01 16:18:45
date last changed
2021-02-17 06:56:04
@article{90d90826-4083-4249-ba36-36a55d78119d,
  abstract     = {Human bone-marrow-derived mesenchymal stem cells (MSC) are responsible the remodeling of human tissue. However, damaged aortic valves are lack the ability to regenerate which is an active cell-mediated process. Diseased aortic valve remodeling has similarities even to bone formation. In this study, the prerequisites for cultured MSCs to undergo osteoblastic differentiation on aortic valves were explored. An ex vivo model using a human aortic valve microenvironment was developed. The expression of type I procollagen, alkaline phosphatase activity, osteocalcin secretion and osteocalcin immunostaining were studied to evaluate the induction of osteogenesis of the MSCs on noncalcified and calcified human aortic valves. Aortic valves were exposed to freeze-thaw injury to devitalize valves in order to separately study the role of valve matrix vs. endothelial cells in the explants. Thus, valves were assigned to 1 of 4 treatment groups: noncalcified uninjured valves, calcified uninjured valves, noncalcified injured and calcified injured. Finally, valves were decalcified to separately explore the effect of a calcified matrix on the osteogenesis. In this co-culture system, the noncalcified uninjured valves inhibited osteogenesis of MSCs, whereas the calcified valves promoted differentiation towards osteoblastic lineage. Devitalization of the valve matrix inflicted a significant increase in the osteogenesis of co-cultured MSCs. Calcified matrix in the valves seemed to have a role in the spontaneous osteogenesis of the MSCs. This spontaneous matrix induced differentiation of MSCs into osteoblast lineage could not be inhibited by pravastatin, indomethacin or tetracycline. In conclusion, these results suggest that interactions between MSCs and aortic valve matrix components and cells modulate MSC phenotype in this environment. Further studies are required to characterize this interesting phenomenon in greater detail.},
  author       = {Leskela, Hannu-Ville and Satta, Jari and Oiva, Jani and Eriksen, Heidi and Juha, Risteli and Korkiamaki, Paula and Ivaska, Kaisa and Soini, Ylermi and Lehenkari, Petri},
  issn         = {1095-8584},
  language     = {eng},
  number       = {4},
  pages        = {642--649},
  publisher    = {Elsevier},
  series       = {Journal of Molecular and Cellular Cardiology},
  title        = {Calcification and cellularity in human aortic heart valve tissue determine the differentiation of bone-marrow-derived cells},
  url          = {http://dx.doi.org/10.1016/j.yjmcc.2006.07.014},
  doi          = {10.1016/j.yjmcc.2006.07.014},
  volume       = {41},
  year         = {2006},
}