Osteogenic abilities of bone marrow stromal cells are not defective in patients with osteonecrosis

Yoo, Jeong Joon; Song, Won Seok; Koo, Kyung‐Hoi; Yoon, Kang Sup; Kim, Hee Joong

doi:10.1007/s00264-008-0524-0

Cited by 17 publications

(13 citation statements)

References 22 publications

(41 reference statements)

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“…Previous data from Yoo et al . described the good osteogenic abilities in vitro of BMSCs from patients with osteonecrosis [ 45 ]. Altogether, these data indicate that the use of autologous BMSCs for a therapeutic treatment of ONFH is a feasible strategy.…”

Section: Discussionmentioning

confidence: 99%

Development of a simple procedure for the treatment of femoral head osteonecrosis with intra-osseous injection of bone marrow mesenchymal stromal cells: study of their biodistribution in the early time points after injection

et al. 2015

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IntroductionOsteonecrosis of the femoral head (ONFH) is a degenerative disease progressing to a femoral head (FH) collapse. Injection of osteoprogenitor cells like bone marrow mesenchymal stromal cells (BMSCs) into the FH appears to be a good therapeutic treatment. However, safety and efficacy of BMSCs to treat bone defect are the main preclinical data required for clinical application. Efficacy and the lack of risk of cell transformation after amplification of BMSCs have been extensively described. The main objectives of this study were to develop a simple and usable procedure for clinicians and control its feasibility by evaluating the biodistribution of BMSCs after injection into the FH in a large animal model. The impact of this approach was evaluated on one natural pig ONFH.MethodsBMSCs were directly injected in the pig FH, and then the biodistribution of grafted cells was detected by quantitative real-time polymerase chain reaction, cytometry, or a combination of classic histology analysis and in situ hybridization (ISH). BMSC efficacy on bone regeneration was evaluated by magnetic resonance imaging (MRI) and histology.ResultsAfter 30-minute and 24-hour follow-up, grafted cells were detected at the injection site and no BMSCs were detected in filter organs or body fluids. The combination of classic histology analysis and ISH showed a good homogeneity of cell distribution in FH. Local delivery of BMSCs onto a bone scaffold associated with bone formation in vivo confirmed the preferential tropism of BMSCs to the bone tissue as well as their efficacy to form bone. Treatment of a natural pig ONFH by autologous BMSCs indicated a beginning of bone healing as early as 2 weeks with a complete healing after 9 weeks. At this stage, MRI and histological analysis were similar to those of a normal FH.ConclusionsIntra-osseous injection of BMSCs in FH seems to be a good strategy for ONFH treatment as the safety concerning the biodistribution of BMSCs is ensured. Moreover, the efficacy of BMSCs in natural ONFH seems to indicate that this is a promising approach. Altogether, these results constitute the preclinical data necessary for the setup of a clinical application with expanded BMSCs in the context of advanced therapy medicinal products.

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Section: Discussionmentioning

confidence: 99%

Development of a simple procedure for the treatment of femoral head osteonecrosis with intra-osseous injection of bone marrow mesenchymal stromal cells: study of their biodistribution in the early time points after injection

et al. 2015

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“…Some previous researches confirmed that the good osteogenic function of BMSCs is existence about patients with alcohol-induced ONFH [ 21 , 22 ]. Our research aimed to explore the affection power of genetic factors for alcohol-induced ONFH.…”

Section: Discussionmentioning

confidence: 94%

Association between alcohol-induced osteonecrosis of femoral head and risk variants ofMMPSin Han population based on a case-control study

Wang

Shi²,

Yang³

et al. 2017

Oncotarget

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The study aimed to evaluate the association between MMP gene superfamily and alcohol-induced osteonecrosis of femoral head (alcohol-induced ONFH) risk given its high prevalence, poor therapeutic effect, and serious clinical prognosis. 308 subjects (mean age, 49.47 years; males, 64.0%) who participated in our control group and 300 alcohol-induced ONFH patients (mean age, 43.29 years; males, 99.7%) formed the case group was enrolled to estimate by statistical analysis. We selected 23 single nucleotide polymorphisms (SNPs) from MMPs, and performed the chi-squared test, Fisher's exact test, t-test and genetic model analyses. From the result, rs243849 which located in MMP2 were 1.355 (1.014-1.811), 1.34 (1.01-1.78) in allele model and log-addictive model, respectively. And the p-value of rs243849 in Cochran-Armitage trend test is 0.044. Unfortunately, the similar results of these SNPs were not observed when adjusted by gender and age. Our study is not enough to supply a positive result to benefit for alcohol-induced ONFH clinical prevention, but guide out a new direction for further experiment.

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“…H-1101-108-353) using a modification of the procedure described by Pittenger et al 32,33 To prepare the CM from hUCB-MSCs, the cells were detached upon reaching 80% confluency in a 9-cm 2 dish and transferred into an a-minimum essential medium (MEM) containing 2% fetal bovine serum (FBS). After incubation for 24 h, the supernatant was collected and sterilized by the passage through a 0.45-mm-pore filter.…”

Section: Isolation and Culture Of Hucb-mscs And Preparation Of CMmentioning

confidence: 99%

Transplantation of Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells or Their Conditioned Medium Prevents Bone Loss in Ovariectomized Nude Mice

Park

Song

et al. 2013

Tissue Engineering Part A

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Umbilical cord blood (UCB) has recently been recognized as a new source of mesenchymal stem cells (MSCs) for use in stem cell therapy. We studied the effects of systemic injection of human UCB-MSCs and their conditioned medium (CM) on ovariectomy (OVX)-induced bone loss in nude mice. Ten-week-old female nude mice were divided into six groups: Sham-operated mice treated with vehicle (Sham-Vehicle), OVX mice subjected to UCBMSCs (OVX-MSC), or human dermal fibroblast (OVX-DFB) transplantation, OVX mice treated with UCB-MSC CM (OVX-CM), zoledronate (OVX-Zol), or vehicle (OVX-Vehicle). Although the OVX-Vehicle group exhibited significantly less bone mineral density (BMD) gain compared with the Sham-Vehicle group, transplantation of hUCB-MSCs (OVX-MSC group) has effectively prevented OVX-induced bone mass attenuation. Notably, the OVX-CM group also showed BMD preservation comparable to the OVX-MSC group. In addition, microcomputed tomography analysis demonstrated improved trabecular parameters in both the OVX-MSC and OVX-CM groups compared to the OVX-Vehicle or OVX-DFB group. Histomorphometric analysis showed increased bone formation parameters, accompanied by increased serum procollagen type-I N-telopeptide levels in OVX-MSC and OVX-CM mice. However, cell-trafficking analysis failed to demonstrate engraftment of MSCs in bone tissue 48 h after cell infusion. In vitro, hUCB-MSC CM increased alkaline phosphatase (ALP) activity in human bone marrow-derived MSCs and mRNA expression of collagen type 1, Runx2, osterix, and ALP in C3H10T1/2 cells. Furthermore, hUCB-MSC CM significantly increased survival of osteocyte-like MLO-Y4 cells, while it inhibited osteoclastic differentiation. To summarize, transplantation of hUCB-MSCs could effectively prevent OVX-mediated bone loss in nude mice, which appears to be mediated by a paracrine mechanism rather than direct engraftment of the MSCs.

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Osteogenic abilities of bone marrow stromal cells are not defective in patients with osteonecrosis

Cited by 17 publications

References 22 publications

Development of a simple procedure for the treatment of femoral head osteonecrosis with intra-osseous injection of bone marrow mesenchymal stromal cells: study of their biodistribution in the early time points after injection

Development of a simple procedure for the treatment of femoral head osteonecrosis with intra-osseous injection of bone marrow mesenchymal stromal cells: study of their biodistribution in the early time points after injection

Association between alcohol-induced osteonecrosis of femoral head and risk variants ofMMPSin Han population based on a case-control study

Transplantation of Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells or Their Conditioned Medium Prevents Bone Loss in Ovariectomized Nude Mice

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