Experimental Study of 3D-TableTrix Microcarriers Loaded with Low-dose Bone Marrow Mesenchymal Stem Cells for the Treatment of Early Osteonecrosis of the Femoral Head

Author:

Guo Minzheng1ORCID,Qi Baochuang2,Pei Zijie1,Ni Haonan3,Ren Junxiao4,Luo Huan2,Shi Hongxin5,Meng Chen2,Rao Yu2,Tang Zhifang5,Pu Luqiao6,Xue Qingyun7,Xu Yongqing6,Li Chuan8ORCID

Affiliation:

1. Chinese Academy of Medical Sciences & Peking Union Medical College

2. Kunming Medical University

3. Affiliated Hospital of Huzhou Normal University: Huzhou Central Hospital

4. Yunnan University of Traditional Chinese Medicine

5. Dali University

6. People's Liberation Army Joint Logistic Support Force 920th Hospital

7. Beijing Hospital

8. Kunming Institute of Zoology Chinese Academy of Sciences

Abstract

Abstract Background Early treatment of ONFH (osteonecrosis of the femoral head) has posed a significant challenge for clinicians. Recent attention has been directed towards stem cell therapy, with BMSCs (bone marrow mesenchymal stem cells) emerging as a potential solution for early-stage ONFH due to their unique capabilities. However, traditional cell injection methods have been associated with unsatisfactory results attributed to issues such as mechanical damage during injection, low cell survival rates, limited cell matrix accumulation, and absence of cellular interactions. To address these concerns, this study utilized a novel cell carrier material called 3D-TableTrix Microcarriers capable of loading BMSCs. Methods Through imaging, serological, and histological analyses, low-dose BMSC-loaded Microcarriers were intravenously injected into a rat model of early-stage hormone-induced osteonecrosis of the femoral head. Repair outcomes were compared to those obtained from high-dose BMSC injections to evaluate the efficacy and safety of this improved strategy. Additionally, a co-culture system study was conducted, in which human primary osteoblasts were seeded in the lower layer, while 3D-TableTrix Microcarrier-loaded human BMSCs or monolayer-cultured human BMSCs were seeded in the upper layer. Phenotypic analysis of the co-cultured human osteoblasts focused on comparing the effects of different BMSC cultivation methods. Results The Microcarriers containing low-dose BMSCs demonstrated comparable repair outcomes to high-dose BMSC injections in the rat model of early-stage hormone-induced osteonecrosis of the femoral head, while minimizing the associated risks of high-dose stem cell administration. Furthermore, the co-culture system revealed that the osteoblasts in the 3D group exhibited a superior phenotype compared to the monolayer-cultured group. Gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis provided insights into the mechanisms underlying the therapeutic effects of 3D Microcarriers loaded with BMSCs in early-stage hormone-induced osteonecrosis of the femoral head. Conclusions This study confirms that 3D-TableTrix Microcarriers loaded with BMSCs offer a promising cellular therapy for early-stage hormone-induced osteonecrosis of the femoral head, potentially achieving efficient treatment outcomes with minimal cell dosages. The improved strategy addresses challenges associated with traditional cell injection methods and highlights the potential of BMSC-loaded Microcarriers to improve the management of early-stage ONFH.

Publisher

Research Square Platform LLC

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