CD146+ skeletal stem cells from growth plate exhibit specific chondrogenic differentiation capacity in vitro

Wu, Yuze; Jing, Xingzhi; Sun, Yue; Ye, Yaping; Guo, Jiachao; Huang, Jian; Xiang, Wei; Zhang, Jiaming; Guo, Fengjing

doi:10.3892/mmr.2017.7616

Cited by 12 publications

(8 citation statements)

References 53 publications

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“…Our data suggest that the loss of surface CD146 marks a gradual transition of BMSCs towards osteochondrogenesis, whereas a gain of CD56 marks a further osteogenic commitment step, which ultimately manifests itself as an accumulation of osteoblasts and immature osteocytes in CD56 cell-rich areas of OA bone. In a recent study, magnetically-sorted CD146+ cells from the rat growth plate exhibited high chondrogenic differentiation capacity in vitro, compared to CD105+ cells 44 . Their seemingly different results to our work could be explained by studying different species (human versus rat), tissue sources (trabecular bone versus the growth plate) and control subpopulations (CD56+ versus CD105+).…”

Section: Discussionmentioning

confidence: 96%

The osteogenic commitment of CD271+CD56+ bone marrow stromal cells (BMSCs) in osteoarthritic femoral head bone

Ilas

Baboolal

Churchman

et al. 2020

Sci Rep

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Osteoarthritis (OA), the most common joint disorder, is characterised by progressive structural changes in both the cartilage and the underlying subchondral bone. In late disease stages, subchondral bone sclerosis has been linked to heightened osteogenic commitment of bone marrow stromal cells (BMSCs). This study utilised cell sorting and immunohistochemistry to identify a phenotypically-distinct, osteogenically-committed BMSC subset in human OA trabecular bone. Femoral head trabecular bone tissue digests were sorted into CD45-CD271+CD56+CD146-, CD45-CD271+CD56-CD146+ and CD45-CD271+CD56-CD146-(termed double-negative, DN) subsets, and CD45+CD271-hematopoietic-lineage cells served as control. Compared to the CD146+ subset, the CD56+ subset possessed a lower-level expression of adipocyte-associated genes and significantly over 100-fold higher-level expression of many osteoblast-related genes including osteopontin and osteocalcin, whilst the DN subset presented a transcriptionally 'intermediate' BMSC population. All subsets were tri-potential following culture-expansion and were present in control non-OA trabecular bone. However, while in non-OA bone CD56+ cells only localised on the bone surface, in OA bone they were additionally present in the areas of new bone formation rich in osteoblasts and newly-embedded osteocytes. In summary, this study reveals a distinct osteogenically-committed CD271+CD56+ BMSC subset and implicates it in subchondral bone sclerosis in hip OA. CD271+CD56+ subset may represent a future therapeutic target for OA and other bone-associated pathologies. Osteoarthritis (OA) is now recognised as a disease of the whole joint characterised by pathological changes to cartilage, subchondral bone and the synovium 1,2. While the site of initiation is still unclear, subchondral bone changes are an important feature in OA pathophysiology 3. Given the high numbers of bone marrow stromal cells (BMSCs) in the subchondral bone 4-6 , their homeostatic role in health, as well as their potential contribution to the endogenous repair mechanisms in OA is currently an area of considerable interest. Recent studies in OA animal models 7 and in human OA 8,9 point towards an altered commitment of BMSCs in OA progression. BMSCs have been long described as a heterogeneous population of cells 10,11 however, no specific markers capable of identifying and segregating differently-committed BMSC subsets in healthy or OA-affected bone have so far been found. Currently, CD271 is considered as one of the characteristic markers for native human BMSC 12-15. We have previously shown an accumulation of CD271+ BMSCs in the damaged femoral head areas of hip OA patients marked by the presence of bone marrow lesions 8 , which are also known to be associated with cartilage loss and bone sclerosis 16. More recently, we have provided further evidence for increased osteogenic activity in OA subchondral bone, implicating both BMSCs and their terminally differentiated progeny osteocytes in hip OA microstructural changes 9. Specifically, the ...

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Section: Discussionmentioning

confidence: 96%

The osteogenic commitment of CD271+CD56+ bone marrow stromal cells (BMSCs) in osteoarthritic femoral head bone

Ilas

Baboolal

Churchman

et al. 2020

Sci Rep

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“…The relationship between the level of CD146 or SSEA4 and lineage differentiation is debatable. CD146+ chondroprogenitors in late‐stage osteoarthritis or skeletal stem cells from the growth plate exhibited higher chondrogenic differentiation capacity . Fluorescence activated enrichment of CD146+ human BMSCs during expansion augmented GAG/DNA content but had no effect on adipogenesis .…”

Section: Discussionmentioning

confidence: 99%

Liver Kinase B1 Fine‐Tunes Lineage Commitment of Human Fetal Synovium‐Derived Stem Cells

Zhou

Zhang

et al. 2019

Journal Orthopaedic Research

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Liver kinase B1 (LKB1), a serine/threonine protein, is a key regulator in stem cell function and energy metabolism. Herein, we describe the role of LKB1 in modulating the differentiation of synovium-derived stem cells (SDSCs) toward chondrogenic, adipogenic, and osteogenic lineages. Human fetal SDSCs were transduced with CRISPR associated protein 9 (Cas9)-single-guide RNA vectors to knockout or lentiviral vectors to overexpress the LKB1 gene. Analyses including ICE (Inference of CRISPR Edits) data from Sanger sequencing and quantitative polymerase chain reaction (qPCR) as well as Western blot demonstrated successful knockout (KO) or overexpression (OE) of LKB1 in human fetal SDSCs without any detectable side effects in morphology, proliferation rate, and cell cycle. LKB1 KO increased CD146 expression; interestingly, LKB1 OE increased SSEA4 level. The qPCR data showed that LKB1 KO upregulated the levels of SOX2 and NANOG while LKB1 OE lowered the expression of POU5F1 and KLF4. Furthermore, LKB1 KO enhanced, and LKB1 OE inhibited, chondrogenic and adipogenic differentiation potential. However, perhaps due to the inherent inability to achieve osteogenesis, LKB1 did not obviously affect osteogenic differentiation. These data demonstrate that LKB1 plays a significant role in determining human SDSCs' adipogenic and chondrogenic differentiation, which might provide an approach for fine-tuning the direction of stem cell differentiation in tissue engineering and regeneration.

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“…However, a gold standard combination of markers has not been definitively agreed upon. Researchers have mainly investigated such markers in rodents [82,83,85] but occasionally human fetal limb [86] or adult joints [87] have been the source. A list of potential markers for the identification of overall skeletal progenitors as well as osteogenic and chondrogenic progenitors is reported in Table 3.…”

Section: Cell Selectionmentioning

confidence: 99%

Pluripotent stem cells for skeletal tissue engineering

Ferreira

Humphreys

Ogene

et al. 2021

Critical Reviews in Biotechnology

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Here, we review the use of human pluripotent stem cells for skeletal tissue engineering. A number of approaches have been used for generating cartilage and bone from both human embryonic stem cells and induced pluripotent stem cells. These range from protocols relying on intrinsic cell interactions and signals from co-cultured cells to those attempting to recapitulate the series of steps occurring during mammalian skeletal development. The importance of generating authentic tissues rather than just differentiated cells is emphasized and enabling technologies for doing this are reported. We also review the different methods for characterization of skeletal cells and constructs at the tissue and single-cell level, and indicate newer resources not yet fully utilized in this field. There have been many challenges in this research area but the technologies to overcome these are beginning to appear, often adopted from related fields. This makes it more likely that cost-effective and efficacious human pluripotent stem cell-engineered constructs may become available for skeletal repair in the near future.

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CD146+ skeletal stem cells from growth plate exhibit specific chondrogenic differentiation capacity in vitro

Cited by 12 publications

References 53 publications

The osteogenic commitment of CD271+CD56+ bone marrow stromal cells (BMSCs) in osteoarthritic femoral head bone

The osteogenic commitment of CD271+CD56+ bone marrow stromal cells (BMSCs) in osteoarthritic femoral head bone

Liver Kinase B1 Fine‐Tunes Lineage Commitment of Human Fetal Synovium‐Derived Stem Cells

Pluripotent stem cells for skeletal tissue engineering

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