Modeling the human bone marrow niche in mice: From host bone marrow engraftment to bioengineering approaches

Abarrategi, Ander; Mian, Syed A; Passaro, Diana; Rouault-Pierre, Kevin; Grey, William; Bonnet, Dominique

doi:10.1084/jem.20172139

Cited by 105 publications

(81 citation statements)

References 205 publications

(286 reference statements)

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“…As one of the biggest and most complex organ systems in mammals, the skeleton is full of cracks and undergoes continuous shaping, remodelling and repair throughout adulthood . Bone can self‐heal robustly in most cases; however, accelerating bone regeneration to meet clinical need would be advantageous . Bone regeneration is a highly complex and temporally coordinated process comprising various cellular and molecular processes …”

Section: Introductionmentioning

confidence: 99%

Ophiopogonin D promotes bone regeneration by stimulating CD31^hiEMCN^hi vessel formation

Yang

Xiao

et al. 2020

Cell Proliferation

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Objectives CD31hiEMCNhi vessels (CD31, also known as PECAM1 [platelet and endothelial cell adhesion molecule 1]; EMCN, endomucin), which are strongly positive for CD31 and endomucin, couple angiogenesis and osteogenesis. However, the role of CD31hiEMCNhi vessels in bone regeneration remains unknown. In the present study, we investigated the role of CD31hiEMCNhi vessels in the process of bone regeneration. Materials and Methods We used endothelial‐specific Krüppel like factor 3 (Klf3) knockout mice and ophiopogonin D treatment to interfere with CD31hiEMCNhi vessel formation. We constructed a bone regeneration model by surgical ablation of the trabecular bone. Immunofluorescence and micro‐computed tomography (CT) were used to detect CD31hiEMCNhi vessels and bone formation. Results CD31hiEMCNhi vessels participate in the process of bone regeneration, such that endothelial‐specific Klf3 knockout mice showed increased CD31hiEMCNhi vessels and osteoprogenitors in the bone regeneration area, and further accelerated bone formation. We also demonstrated that the natural compound, ophiopogonin D, acts as a KLF3 inhibitor to promote vessels formation both in vitro and in vivo. Administration of ophiopogonin D increased the abundance of CD31hiEmcnhi vessels and accelerated bone healing. Conclusions Our findings confirmed the important role of CD31hiEmcnhi vessels in bone regeneration and provided a new target to treat bone fracture or promote bone regeneration.

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Section: Introductionmentioning

confidence: 99%

Ophiopogonin D promotes bone regeneration by stimulating CD31^hiEMCN^hi vessel formation

Yang

Xiao

et al. 2020

Cell Proliferation

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“…Osteoporosis is caused by bone resorption that exceeds bone formation . Considering that the mutation of IGSF23 inhibited the osteoclast differentiation, which indicates that inhibition of IGSF23 may be regarded as a putative strategy for treating osteoporosis.…”

Section: Resultsmentioning

confidence: 99%

“…Osteoporosis is caused by bone resorption that exceeds bone formation. [34][35][36] Considering that the mutation of IGSF23 inhibited the osteoclast differentiation, which indicates that inhibition of IGSF23 may be regarded as a putative strategy for treating osteoporosis. To investigate the therapeutic effects of silencing IGSF23 in osteoclast differentiation, adeno-associated virus (AAV)-shIGSF23 was injected into the femoral bone marrow cavity of OVX mice twice per month for 3 months (n = 6).…”

Section: Silencing Of Igsf23 Reversed the Bone Loss In Ovx Micementioning

confidence: 99%

Osteoclastogenesis inhibition by mutated IGSF23 results in human osteopetrosis

et al. 2019

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Objectives Osteopetrosis is a rare inherited skeletal disease characterized by increased bone mineral density due to the loss of osteoclast function or differentiation potential. Materials and Methods The study involved a Chinese patient with osteopetrosis (the proband) and her immediate family members and 180 controls without osteopetrosis. Bone density of the femoral neck, lumbar spine and total body was measured using dual‐energy x‐ray absorptiometry. Osteoclast differentiation by the participants’ peripheral blood mononuclear cells (PBMCs) was investigated using tartrate‐resistant acid phosphatase (TRAP) staining. Osteoblast differentiation was examined with Alizarin Red S staining. Reverse transcription‐quantitative PCR was used to amplify immunoglobulin superfamily member 23 (IGSF23), c‐FOS and nuclear factor of activated T cells 1 (NFATC1). Results We found a homozygous mutation (c.295C>T) in the IGSF23 gene in two osteopetrosis samples. The mutation led to the formation of a stop codon, causing loss of the immunoglobulin‐like domain and the whole transmembrane domain. PBMCs from the proband (IGSF23−/−) exhibited poor ability for differentiating into mature osteoclasts in vitro. Overexpression of IGSF23 rescued the ability of IGSF23−/− PBMCs to differentiate into osteoclasts. Moreover, knockdown of IGSF23 reversed the bone loss in OVX mice by injecting AAV‐shIGSF23 into mice femoral bone marrow cavity. Furthermore, we also found that the IGSF23 mutation led to decreased c‐Fos and NFATC1 expression levels by inhibiting the mitogen‐activated protein kinase signalling pathways. Conclusions IGSF23‐mediated osteoclast differentiation of PBMCs may serve as a potential target in osteoporosis therapy.

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“…Increasingly immunocompromised mouse strains on the nonobese diabetic (NOD) genetic background have been developed as a means to improve long-term engraftment of both normal and malignant haematopoietic cells [100][101][102][103]. Increasingly immunocompromised mouse strains on the nonobese diabetic (NOD) genetic background have been developed as a means to improve long-term engraftment of both normal and malignant haematopoietic cells [100][101][102][103].…”

Section: Discussionmentioning

confidence: 99%

“…The initial experiments showing multilineage human haematopoietic engraftment of immunocompromised mice were thought of as research and development of in vivo tools to study blood malignancies, not HSCs [102,104,105]. SCID mice, derived from a spontaneous mutation on the Pkrdc locus that resulted in a marked decrease in T and B cells [106], were in fact instrumental for the discovery of initiating cells in acute myeloid leukaemia [107].…”

Section: Discussionmentioning

confidence: 99%

Haematopoietic stem cell reprogramming and the hope for a universal blood product

2019

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Edited by Catherine RobinHaematopoietic stem cells (HSCs) are the only adult stem cells with a demonstrated clinical use, even though a tractable method to maintain and expand human HSCs in vitro has not yet been found. Owing to the introduction of transplantation strategies for the treatment of haematological malignancies and, more recently, the promise of gene therapy, the need to improve the generation, manipulation and scalability of autologous or allogeneic HSCs has risen steeply over the past decade. In that context, reprogramming strategies based on the expression of exogenous transcription factors have emerged as a means to produce functional HSCs in vitro. These approaches largely stem from the assumption that key master transcription factors direct the expression of downstream target genes thereby triggering haematopoiesis. Both somatic and pluripotent cells have been used to this end, yielding variable results in terms of haematopoietic phenotype and functionality. Here, we present an overview of the haematopoietic reprogramming methods reported to date, provide the appropriate historical context and offer some critical insight about where the field stands at present.

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Modeling the human bone marrow niche in mice: From host bone marrow engraftment to bioengineering approaches

Abstract: Abarrategi et al. summarize the methods used for human hematopoietic cell xenotransplantation and their milestones. They also discuss the latest approaches in generating humanized BM tissues in mice to study human normal and malignant hematopoiesis.

Cited by 105 publications

References 205 publications

Ophiopogonin D promotes bone regeneration by stimulating CD31^hiEMCN^hi vessel formation

Ophiopogonin D promotes bone regeneration by stimulating CD31^hiEMCN^hi vessel formation

Osteoclastogenesis inhibition by mutated IGSF23 results in human osteopetrosis

Haematopoietic stem cell reprogramming and the hope for a universal blood product

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Modeling the human bone marrow niche in mice: From host bone marrow engraftment to bioengineering approaches

Abstract: Abarrategi et al. summarize the methods used for human hematopoietic cell xenotransplantation and their milestones. They also discuss the latest approaches in generating humanized BM tissues in mice to study human normal and malignant hematopoiesis.

Cited by 105 publications

References 205 publications

Ophiopogonin D promotes bone regeneration by stimulating CD31hiEMCNhi vessel formation

Ophiopogonin D promotes bone regeneration by stimulating CD31hiEMCNhi vessel formation

Osteoclastogenesis inhibition by mutated IGSF23 results in human osteopetrosis

Haematopoietic stem cell reprogramming and the hope for a universal blood product

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Product

Resources

About

Ophiopogonin D promotes bone regeneration by stimulating CD31^hiEMCN^hi vessel formation

Ophiopogonin D promotes bone regeneration by stimulating CD31^hiEMCN^hi vessel formation