Treatment of femoral head osteonecrosis with advanced cell therapy in sheep

Vélez, Roberto; Hernández-Fernández, Alberto; Caminal, Marta; Vives, Joaquim; Soldado, Francisco; Fernández, Alejandro; Pla, Arnau; Useche, María Cristina

doi:10.1007/s00402-012-1584-6

Cited by 21 publications

(22 citation statements)

References 36 publications

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“…Osteoblasts, common in the growth of bone tissue, gather in the newly formed bone surface, and have an important role in the process of bone tissue development, bone metabolism and bone mass balance maintenance and damage repair (7)(8)(9). Femoral head necrosis is a common intractable clinical orthopedic disease, and previous studies found that it may be closely associated with the dysfunction of osteoblasts and bone marrow stromal cells (10)(11)(12). The mechanism is that bone marrow stromal cells differentiate into adipocytes, and hormones regulate bone marrow stem cell differentiation into fat cells.…”

Section: Discussionmentioning

confidence: 98%

Mechanism of chlorogenic acid treatment on femoral head necrosis and its protection of osteoblasts

Zhang

2016

Biomedical Reports

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The aim of the present study was to investigate the therapeutic effect of chlorogenic acid on hormonal femoral head necrosis and its protection of osteoblasts. The study established a femoral head necrosis model in Wistar rats using endotoxin and prednisolone acetate. The rats were divided into five groups and were treated with different concentrations of chlorogenic acid (1, 10 and 20 mg/kg). The main detected indicators were the blood rheology, bone mineral density, and the hydroxyproline and hexosamine (HOM) contents. At a cellular level, osteoblasts were cultured and treated by drug-containing serum. Subsequently, cell proliferation and the osteoblast cycle were measured using flow cytometry, and the protein expression levels of Bax and B-cell lymphoma 2 (Bcl-2) were detected using western blotting. Chlorogenic acid at a concentration of 20 mg/kg (high-dose) enhanced the bone mineral density of the femoral head and femoral neck following ischemia. Simultaneously, blood flow following the injection of prednisolone acetate was significantly improved, and the HOM contents of the high-dose chlorogenic acid group were significantly different. The results from the flow cytometry analysis indicated that chlorogenic acid can efficiently ameliorate hormone-induced necrosis. The osteoblasts were isolated and cultured. The MTT colorimetric assay showed that chlorogenic acid at different densities can increase the proliferation capabilities of osteoblasts and accelerate the transition process of G/G phase to S phase, as well as enhance mitosis and the regeneration of osteoblasts. Western blotting detection indicated that chlorogenic acid may prohibit the decrease of Bcl-2 and the increase of Bax during apoptosis, thereby inhibiting osteoblast apoptosis and preventing the deterioration of femoral head necrosis. In conclusion, chlorogenic acid at the density of 20 mg/kg is effective in the treatment of hormonal femoral head necrosis, which may be applicable for future treatment.

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Section: Discussionmentioning

confidence: 98%

Mechanism of chlorogenic acid treatment on femoral head necrosis and its protection of osteoblasts

Zhang

2016

Biomedical Reports

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“…[23][24][25] Furthermore, quite a number studies have manifested that transplanted autologous or allogeneic MSCs were capable of survival, proliferation, and differentiation into osteoblasts directly in the necrotic femoral head on humans 26-28 and a variety of animal models; for example, in mouse, 29 rabbit, 30,31 dog, 32 and sheep. 33 Thus, regulation on the osteogenesis and adipogenesis of MSCs is the novel therapeutics for ONFH treatment. Therefore, we explored the molecular mechanism by which HG impacts the function of ONFH during MSC differentiation.…”

Section: Discussionmentioning

confidence: 99%

Aqueous Fraction of Huogu Formula Promotes Osteogenic Differentiation of Bone Marrow Stromal Cells Through the BMP and Wnt Signaling Pathways

Kong

Zhang

et al. 2016

Rejuvenation Research

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Our recent studies have shown that Huogu (HG) formula was effective both in clinic experience and in experimental osteonecrosis of the femoral head (ONFH). Given that defective of bone marrow stromal cells (MSCs) contribute to the development of osteonecrosis and MSCs show enormous potential in the treatment of ONFH, especially to aging people. How HG impacts the differentiation of MSCs and what is the underlying cellular and molecular mechanism remains largely unknown. Here, we found that an aqueous fraction of HG (HGA) significantly increased the alkaline phosphatase (ALP) activity, mineralized nodules, and migration of MSCs in a dose-dependent manner. Meanwhile, HGA could enhance the mRNA and protein expression of Runt-related transcription factor 2 (Runx2), Alp, Bmp2, osteocalcin (Ocn), and Osterix (Osx). Further investigation of the molecular mechanisms revealed that HGA treatment obviously increased expression, secretion, and activation of bone morphogenetic protein (BMP) 2 and b-catenin, two key regulators of the BMP or Wnt signaling pathway. Furthermore, osteogenic differentiation of MSCs could be blocked by using pharmacological inhibitors for these signaling pathways such as Noggin and Dkk-1. Besides, HGA could inhibit adipogenic differentiation of MSCs. Our study reveals that HGA promotes the osteogenesis of MSCs via the BMP and Wnt signaling pathways. Our findings provide mechanistic insights into the role of HG in treating ONFH.

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“…This is not only because of the multilineage progenitor potential of MSCs, but also because of their capacity to modulate the host microenvironment by secreting a variety of factors, such as cytokines, chemokines or growth factors, which can mediate diverse functions via crosstalk between different cell types (Friedenstein et al, ; Doorn et al, ; Murphy et al, ). Examples of using sheep as a model system include spinal fusion (Goldschlager et al, ), segmental tibial defects (Niemeyer et al, ), chondral/osteochondral repair (Ahern et al, ; Caminal et al, ,b, ; Vives et al, ), tendon and ligament regeneration (Lacitignola et al, ) and osteonecrosis of the femoral head (Velez et al, ), among others.…”

Section: Introductionmentioning

confidence: 99%

A reproducible method for the isolation and expansion of ovine mesenchymal stromal cells from bone marrow for use in regenerative medicine preclinical studies

Caminal

Vélez

Rabanal

et al. 2016

J Tissue Eng Regen Med

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The use of multipotent mesenchymal stromal cells (MSCs) as candidate medicines for treating a variety of pathologies is based on their qualities as either progenitors for the regeneration of damaged tissue or producers of a number of molecules with pharmacological properties. Preclinical product development programmes include the use of well characterized cell populations for proof of efficacy and safety studies before testing in humans. In the field of orthopaedics, an increasing number of translational studies use sheep as an in vivo test system because of the similarities with humans in size and musculoskeletal architecture. However, robust and reproducible methods for the isolation, expansion, manipulation and characterization of ovine MSCs have not yet been standardised. The present study describes a method for isolation and expansion of fibroblastic-like, adherent ovine MSCs that express CD44, CD90, CD140a, CD105 and CD166, and display trilineage differentiation potential. The 3-week bioprocess proposed here typically yielded cell densities of 1.4 × 10 MSCs/cm at passage 2, with an expansion factor of 37.8 and approximately eight cumulative population doublings. The osteogenic potential of MSCs derived following this methodology was further evaluated in vivo in a translational model of osteonecrosis of the femoral head, in which the persistence of grafted cells in the host tissue and their lineage commitment into osteoblasts and osteocytes was demonstrated by tracking enhanced green fluorescent protein-labelled cells. Copyright © 2016 John Wiley & Sons, Ltd.

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Treatment of femoral head osteonecrosis with advanced cell therapy in sheep

Abstract: Our findings indicate that a BMCSs loaded bone matrix scaffold is capable of stimulating bone regeneration more effectively than isolated core decompression or in association with an acellular scaffold in a preclinical femoral head osteonecrosis model in sheep.

Cited by 21 publications

References 36 publications

Mechanism of chlorogenic acid treatment on femoral head necrosis and its protection of osteoblasts

Mechanism of chlorogenic acid treatment on femoral head necrosis and its protection of osteoblasts

Aqueous Fraction of Huogu Formula Promotes Osteogenic Differentiation of Bone Marrow Stromal Cells Through the BMP and Wnt Signaling Pathways

A reproducible method for the isolation and expansion of ovine mesenchymal stromal cells from bone marrow for use in regenerative medicine preclinical studies

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