Mesenchymal stem cells and porous β-tricalcium phosphate composites prepared through stem cell screen-enrich-combine(−biomaterials) circulating system for the repair of critical size bone defects in goat tibia

Stem Cell Research & Therapy, Jun 2018

Background Efficacious bone substitute is essential for the treatment of a critical size bone defect. Currently, the bone substitutes commonly used in clinical practice lack osteogenic capacity and the therapeutic efficacy is not ideal. Herein, a novel stem cell screen-enrich-combine(−biomaterials) circulating system (SECCS) was introduced to provide the substitutes with osteogenic ability. The stem cell screening, enrichment, and recombination with substitutes could be integrated during the surgical operation. Using SECCS, the bioactive mesenchymal stem cells (MSCs) and porous β-tricalcium phosphate (β-TCP) composites (MSCs/β-TCP) were rapidly prepared for critical size bone defect repair and validated in goat models of critical size tibia defects. Methods Twelve goats with right hind limb tibia defects of 30 mm were randomly divided into two groups: six (the experimental group) were treated with MSCs/β-TCP prepared by SECCS and the other six goats (the control group) were treated with pure porous β-TCP. The repair effect was assessed by x-ray, computed tomography (CT), micro-CT, histology and histomorphology 6 months after the operation. In addition, the enrichment efficacy of MSCs and the characteristics of the MSCs/β-TCP prepared by SECCS were evaluated. Results The SECCS could compound about 81.3 ± 3.0% of the MSCs in bone marrow to the porous β-TCP without affecting the cell viability. The average number of MSCs for retransplantation was 27,655.0 ± 5011.6 for each goat from the experimental group. In vitro, satisfactory biocompatibility of the MSCs/β-TCP was performed, with the MSCs spreading adequately, proliferating actively, and retaining the osteogenic potential. In vivo, the defect repair by MSCs/β-TCP with good medullary cavity recanalization and cortical remodeling was significantly superior to that of pure porous β-TCP. Conclusions The MSCs/β-TCP prepared through SECCS demonstrated significant therapeutic efficacy in goat models of critical size bone defect. This provides a novel therapeutic strategy for critical size bone defects caused by severe injury, infection, and bone tumor resection with a high profile of safety, effectiveness, simplicity, and ease.

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Mesenchymal stem cells and porous β-tricalcium phosphate composites prepared through stem cell screen-enrich-combine(−biomaterials) circulating system for the repair of critical size bone defects in goat tibia

Chu et al. Stem Cell Research & Therapy Mesenchymal stem cells and porous β- tricalcium phosphate composites prepared through stem cell screen-enrich- combine(−biomaterials) circulating system for the repair of critical size bone defects in goat tibia Wenxiang Chu 0 1 Yaokai Gan 0 1 Yifu Zhuang 0 1 Xin Wang 0 1 Jie Zhao 0 1 Tingting Tang 0 1 Kerong Dai 0 1 0 Department of Orthopaedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine , Shanghai 200011 , China 1 Shanghai Key Laboratory of Orthopaedic Implants, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine , Shanghai 200011 , China Background: Efficacious bone substitute is essential for the treatment of a critical size bone defect. Currently, the bone substitutes commonly used in clinical practice lack osteogenic capacity and the therapeutic efficacy is not ideal. Herein, a novel stem cell screen-enrich-combine(−biomaterials) circulating system (SECCS) was introduced to provide the substitutes with osteogenic ability. The stem cell screening, enrichment, and recombination with substitutes could be integrated during the surgical operation. Using SECCS, the bioactive mesenchymal stem cells (MSCs) and porous β-tricalcium phosphate (β-TCP) composites (MSCs/β-TCP) were rapidly prepared for critical size bone defect repair and validated in goat models of critical size tibia defects. Methods: Twelve goats with right hind limb tibia defects of 30 mm were randomly divided into two groups: six (the experimental group) were treated with MSCs/β-TCP prepared by SECCS and the other six goats (the control group) were treated with pure porous β-TCP. The repair effect was assessed by x-ray, computed tomography (CT), micro-CT, histology and histomorphology 6 months after the operation. In addition, the enrichment efficacy of MSCs and the characteristics of the MSCs/β-TCP prepared by SECCS were evaluated. Results: The SECCS could compound about 81.3 ± 3.0% of the MSCs in bone marrow to the porous β-TCP without affecting the cell viability. The average number of MSCs for retransplantation was 27,655.0 ± 5011.6 for each goat from the experimental group. In vitro, satisfactory biocompatibility of the MSCs/β-TCP was performed, with the MSCs spreading adequately, proliferating actively, and retaining the osteogenic potential. In vivo, the defect repair by MSCs/β-TCP with good medullary cavity recanalization and cortical remodeling was significantly superior to that of pure porous β-TCP. Conclusions: The MSCs/β-TCP prepared through SECCS demonstrated significant therapeutic efficacy in goat models of critical size bone defect. This provides a novel therapeutic strategy for critical size bone defects caused by severe injury, infection, and bone tumor resection with a high profile of safety, effectiveness, simplicity, and ease. Critical size bone defects; Mesenchymal stem cells; Enrichment technique; Bone regeneration Background The current procedure for the treatment of critical size bone defects caused by severe injury, infection, bone tumor resection, and congenital deformity is not only challenging but also exhibits unsatisfactory outcomes [ 1–4 ]. Autogenous bone transplantation with effective repair outcome and a high safety profile has been regarded as the golden standard for bone defect repair; however, the limited resource of donor bones and the complications in donor sites such as bleeding and pain have restricted its clinical application [ 5– 7 ]. Bone allografts and the processed products such as demineralized bone matrix have risks for immunological rejection and disease transmission, as well as lower osteogenic capability [ 8, 9 ]. Bioactive ceramic materials with osteoconduction properties such as porous β-tricalcium phosphate (β-TCP) and hydroxyapatite have been widely adopted in clinical practice, but the use of these materials is problematic for the repair of critical size bone defect [ 10–12 ]. Tissue engineering is another strategy for the treatment of critical size bone defects, and the effectiveness of bone engineering with mesenchymal stem cells (MSCs) as seeds for critical size bone defects has been demonstrated in several preclinical studies [ 3, 13–15 ]. Liu et al. [16] successfully repaired a 26-mm tibia defect in a goat model with in-vitro amplified MSCs and β-TCP composite (MSCs/β-TCP). Although satisfactory bone repair has been achieved using bone tissue engineering, the concerns regarding the ethics, safety, high cost, and long-term in-vitro culture have made its use in clinical practice challenging. On the contrary, stem cell enrichment techniques technically avoid the limitations of cell culture and effectively acquire bone marrow MSCs, which are the most critical components for osteogenesis. These could be used for bone repair by either a single injection or a combination with bone substitutes [ 17, 18 ]. Previous reports have demonstrated an efficacy of 9 (...truncated)


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Wenxiang Chu, Yaokai Gan, Yifu Zhuang, Xin Wang, Jie Zhao, Tingting Tang, Kerong Dai. Mesenchymal stem cells and porous β-tricalcium phosphate composites prepared through stem cell screen-enrich-combine(−biomaterials) circulating system for the repair of critical size bone defects in goat tibia, Stem Cell Research & Therapy, 2018, pp. 157, Volume 9, Issue 1, DOI: 10.1186/s13287-018-0906-1