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

Bolander, Johanna; Herpelinck, Tim; Chaklader, Malay; Gklava, Charikleia; Geris, Liesbet; Luyten, Frank P.

doi:10.1002/sctm.19-0151

Cited by 22 publications

(13 citation statements)

References 46 publications

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“…These findings show the importance of appropriate in vitro conditions to achieve good results in vivo. In addition, BMPR2 appears to be a promising biomarker for enriching skeletal progenitor cells to achieve in vivo bone regeneration [ 39 ].…”

Section: Factors That Induce Bone Formationmentioning

confidence: 99%

A Review of Recent Developments in the Molecular Mechanisms of Bone Healing

Rodríguez-Merchán

2021

IJMS

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Between 5 and 10 percent of fractures do not heal, a condition known as nonunion. In clinical practice, stable fracture fixation associated with autologous iliac crest bone graft placement is the gold standard for treatment. However, some recalcitrant nonunions do not resolve satisfactorily with this technique. For these cases, biological alternatives are sought based on the molecular mechanisms of bone healing, whose most recent findings are reviewed in this article. The pro-osteogenic efficacy of morin (a pale yellow crystalline flavonoid pigment found in old fustic and osage orange trees) has recently been reported, and the combined use of bone morphogenetic protein-9 (BMP9) and leptin might improve fracture healing. Inhibition with methyl-piperidino-pyrazole of estrogen receptor alpha signaling delays bone regeneration. Smoking causes a chondrogenic disorder, aberrant activity of the skeleton’s stem and progenitor cells, and an intense initial inflammatory response. Smoking cessation 4 weeks before surgery is therefore highly recommended. The delay in fracture consolidation in diabetic animals is related to BMP6 deficiency (35 kDa). The combination of bioceramics and expanded autologous human mesenchymal stem cells from bone marrow is a new and encouraging alternative for treating recalcitrant nonunions.

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Section: Factors That Induce Bone Formationmentioning

confidence: 99%

A Review of Recent Developments in the Molecular Mechanisms of Bone Healing

Rodríguez-Merchán

2021

IJMS

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“…hPDCs as candidate cells (Roberts et al, 2015;Bolander et al, 2020). We have documented the differences between PDCs obtained from different anatomical locations (maxilla, mandible and tibia, respectively) in vitro and also in vivo.…”

Section: Discussionmentioning

confidence: 99%

“…Ultimately, some data suggests that PDCs contain a higher bone regenerative potential than BM-SSPCs (Duchamp de Lageneste et al, 2018). For these reasons PDCs are increasingly studied as a clinically relevant source for bone tissue engineering purposes (Nakahara et al, 1991;De Bari et al, 2006;van Gastel et al, 2012;Owston et al, 2019;Bolander et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

The Bone-Forming Properties of Periosteum-Derived Cells Differ Between Harvest Sites

Groeneveldt

Herpelinck

Maréchal

et al. 2020

Front. Cell Dev. Biol.

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The development of alternatives for autologous bone grafts is a major focus of bone tissue engineering. To produce living bone-forming implants, skeletal stem and progenitor cells (SSPCs) are envisioned as key ingredients. SSPCs can be obtained from different tissues including bone marrow, adipose tissue, dental pulp, and periosteum. Human periosteum-derived cells (hPDCs) exhibit progenitor cell characteristics and have well-documented in vivo bone formation potency. Here, we have characterized and compared hPDCs derived from tibia with craniofacial hPDCs, from maxilla and mandible, respectively, each representing a potential source for cell-based tissue engineered implants for craniofacial applications. Maxilla and mandible-derived hPDCs display similar growth curves as tibial hPDCs, with equal trilineage differentiation potential toward chondrogenic, osteogenic, and adipogenic cells. These craniofacial hPDCs are positive for SSPC-markers CD73, CD164, and Podoplanin (PDPN), and negative for CD146, hematopoietic and endothelial lineage markers. Bulk RNA-sequencing identified genes that are differentially expressed between the three sources of hPDC. In particular, differential expression was found for genes of the HOX and DLX family, for SOX9 and genes involved in skeletal system development. The in vivo bone formation, 8 weeks after ectopic implantation in nude mice, was observed in constructs seeded with tibial and mandibular hPDCs. Taken together, we provide evidence that hPDCs show different profiles and properties according to their anatomical origin, and that craniofacial hPDCs are potential sources for cell-based bone tissue engineering strategies. The mandible-derived hPDCs display - both in vitro and in vivo - chondrogenic and osteogenic differentiation potential, which supports their future testing for use in craniofacial bone regeneration applications.

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“…In addition, hPL-expanded MSCs were reported to have an enhanced osteogenic and chondrogenic differentiation potential (Jonsdottir-Buch et al 2013;Salvade et al 2010). To address the issues, with interfering ligands, stimulatory factors, and batch-batch inconsistency, a shift toward alternate supplements and chemically defined media (CDM) has been advocated and intensively investigated (Bolander et al 2017(Bolander et al , 2019.…”

Section: In Vitro Expansionmentioning

confidence: 99%

“…In an attempt to further understand the improved regenerative potential by serum free preconditioning of hPDCs, in depth profiling by single-cell RNA sequencing was performed (Bolander et al 2019). Interestingly, preconditioning in CDM was shown to induce a phenotype switch at the single-cell level with elevated expression of markers and signaling clusters associated with skeletal system development, tissue regeneration, stem cell maintenance, cell fate commitment, and the BMP-signaling pathway.…”

mentioning

confidence: 99%

Periosteum Derived Cells in Skeletal Tissue Regeneration

Bolander¹,

Herpelinck²,

Luyten³

2020

Cell Engineering and Regeneration

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The field of skeletal tissue engineering has in recent years been transformed by the identification of specific skeletal progenitor cell populations and their role in bone fracture healing. Specifically, progenitor cells residing within the periosteum have been shown to be crucial for bone regeneration. Importantly, this is not a phenomenon performed by one common progenitor cell, instead, distinct skeletal progenitor cell populations have been identified within the periosteum, shown to also contribute to different aspects of tissue repair. These findings represent major steps in the field of regenerative medicine, since there is currently no reliable treatment for patients with a failing endogenous repair system. Therefore, insights regarding the specific cell populations and factors that steer their homing and differentiation in vivo can aid in the development of optimized and personalized engineered treatment strategies. In this chapter, we highlight the crucial role of periosteumderived cells in bone development, homeostasis, and repair. We next provide an overview of the periosteum-residing skeletal progenitor cells identified so far and their role in bone regeneration. Subsequently, we discuss the required steps to isolate and expand periosteal cells in vitro, and the current state of the art in the use of periosteum-derived cells for bone formation and regeneration following the intramembranous, endochondral, or osteochondral tissue repair route. Finally, we present an overview of periosteal cells in the preclinical and clinical setting and discuss their future potential.

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

Cited by 22 publications

References 46 publications

A Review of Recent Developments in the Molecular Mechanisms of Bone Healing

A Review of Recent Developments in the Molecular Mechanisms of Bone Healing

The Bone-Forming Properties of Periosteum-Derived Cells Differ Between Harvest Sites

Periosteum Derived Cells in Skeletal Tissue Regeneration

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