Single‐cell characterization and metabolic profiling of in vitro cultured human skeletal progenitors with enhanced in vivo bone forming capacity

Autor: Liesbet Geris, Charikleia Gklava, Tim Herpelinck, Frank P. Luyten, Malay Chaklader, Johanna Bolander
Jazyk: angličtina
Rok vydání: 2020
Předmět:
0301 basic medicine
Bone Regeneration
Cell
serum-free
PERIOSTEUM
bone
0302 clinical medicine
Tissue engineering
Cells
Cultured
lcsh:R5-920
Chemistry
lcsh:Cytology
Stem Cells
General Medicine
MORPHOGENETIC PROTEIN
Cell biology
FATE DECISIONS
medicine.anatomical_structure
cell surface markers
tissue engineering
tissue‐specific stem cells
serum‐free
lcsh:Medicine (General)
Life Sciences & Biomedicine
GROWTH-FACTOR
Cell signaling
CALCIUM-PHOSPHATE
tissue regeneration
OSTEOINDUCTION
03 medical and health sciences
Cell & Tissue Engineering
In vivo
Tissue Engineering and Regenerative Medicine
medicine
Animals
Humans
BMP
cell signaling
Progenitor cell
lcsh:QH573-671
Bone regeneration
Science & Technology
RECEPTOR
Cluster of differentiation
mesenchymal stem cells (MSCs)
Cell Biology
BMPR2
tissue-specific stem cells
030104 developmental biology
MARROW
TISSUE
030217 neurology & neurosurgery
Developmental Biology
Zdroj: Stem Cells Translational Medicine, Vol 9, Iss 3, Pp 389-402 (2020)
Stem Cells Translational Medicine
ISSN: 2157-6564
2157-6580
Popis: Cell populations and their interplay provide the basis of a cell-based regenerative construct. Serum-free preconditioning can overcome the less predictable behavior of serum expanded progenitor cells, but the underlying mechanism and how this is reflected in vivo remains unknown. Herein, the cellular and molecular changes associated with a cellular phenotype shift induced by serum-free preconditioning of human periosteum-derived cells were investigated. Following BMP-2 stimulation, preconditioned cells displayed enhanced in vivo bone forming capacity, associated with an adapted cellular metabolism together with an elevated expression of BMPR2. Single-cell RNA sequencing confirmed the activation of pathways and transcriptional regulators involved in bone development and fracture healing, providing support for the augmentation of specified skeletal progenitor cell populations. The reported findings illustrate the importance of appropriate in vitro conditions for the in vivo outcome. In addition, BMPR2 represents a promising biomarker for the enrichment of skeletal progenitor cells for in vivo bone regeneration. Significance statement A critical number of in vitro expanded progenitor cells provide the key driving force in a cell-based regenerative construct. Standard expansion protocols highly affect the initial cellular phenotype due to the focus on fast expansion rather than on the maintenance of the progenitor potential. This article describes a serum-free preconditioning regime of in vitro expanded human periosteum-derived cells that lead to a progenitor cell with enhanced in vivo bone forming capacity at the single cell level. This phenotype shift was associated with an adapted cellular metabolism and activation of pathways and transcriptional regulators involved in bone development and fracture healing, illustrating the importance of appropriate in vitro conditions for the in vivo outcome.
Databáze: OpenAIRE
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