Cyclic hydrostatic pressure promotes a stable cartilage phenotype and enhances the functional development of cartilaginous grafts engineered using multipotent stromal cells isolated from bone marrow and infrapatellar fat pad

Bone marrow-derived multipotent stromal cells (BMMSCs) represent an attractive therapeutic modality for cell therapy in type 2 diabetes mellitus (T2DM)-associated complications. T2DM changes the bone marrow environment; however, its effects on BMMSC properties remain unclear. The present study aimed at investigating select functions and differentiation of BMMSCs harvested from the T2DM microenvironment as potential candidates for regenerative medicine. BMMSCs were obtained from Zucker diabetic fatty (ZDF; an obese-T2DM model) rats and their lean littermates (ZL; controls), and cultured under normoglycemic conditions. The BMMSCs derived from ZDF animals were fewer in number, with limited clonogenicity (by 2-fold), adhesion (by 2.9-fold), proliferation (by 50%), migration capability (by 25%), and increased apoptosis rate (by 2.5-fold) compared to their ZL counterparts. Compared to the cultured ZL-BMMSCs, the ZDF-BMMSCs exhibited (i) enhanced adipogenic differentiation (increased number of lipid droplets by 2-fold; upregulation of the Pparg, AdipoQ, and Fabp genes), possibly due to having been primed to undergo such differentiation in vivo prior to cell isolation, and (ii) different angiogenesis-related gene expression in vitro and decreased proangiogenic potential after transplantation in nude mice. These results provided evidence that the T2DM environment impairs BMMSC expansion and select functions pertinent to their efficacy when used in autologous cell therapies.

Download Full-text

The clinical efficacy of arthroscopic therapy with knee infrapatellar fat pad cell concentrates in treating knee cartilage lesion: a prospective, randomized, and controlled study

Journal of Orthopaedic Surgery and Research ◽

10.1186/s13018-021-02224-9 ◽

2021 ◽

Vol 16 (1) ◽

Author(s):

Yiqin Zhou ◽

Haobo Li ◽

Dong Xiang ◽

Jiahua Shao ◽

Qiwei Fu ◽

...

Keyword(s):

Clinical Efficacy ◽

Mesenchymal Stromal Cells ◽

Stromal Cells ◽

Knee Arthroscopy ◽

Infrapatellar Fat Pad ◽

Control Group ◽

Knee Cartilage ◽

Fat Pad ◽

Group 12 ◽

Significant Difference

Abstract Introduction To evaluate the clinical efficacy of arthroscopic therapy with infrapatellar fat pad cell concentrates in treating knee cartilage lesions, we conducted a prospective randomized single-blind clinical study of controlled method. Methods Sixty cases from Shanghai Changzheng Hospital from April 2018 to December 2019 were chosen and randomly divided into 2 groups equally. Patients in the experiment group were treated through knee arthroscopy with knee infrapatellar fat pad cell concentrates containing mesenchymal stromal cells, while patients in the control group were treated through regular knee arthroscopic therapy. VAS and WOMAC scores were assessed at pre-operation, and 6 weeks, 12 weeks, 6 months, and 12 months after intervention. MORCART scores were assessed at pre-operation and 12 months after intervention. Results Twenty-nine cases in the experiment group and 28 cases in the control group were followed up. No significant difference in VAS, WOMAC, and MOCART scores were found between the two groups before surgery (P > 0.05). The WOMAC total and WOMAC function scores of the experiment group were significantly lower than those of the control group 6 months and 12 months after surgery (P < 0.05). The VAS rest and VAS motion scores of the experiment group were found significantly lower than those of the control group 12 months after surgery (P < 0.05). The MOCART scores of the experiment group were found significantly higher compared with the control group 12 months after surgery (P < 0.05). No significant difference in WOMAC stiffness scores were found between the two groups. Conclusions The short-term results of our study are encouraging and demonstrate that knee arthroscopy with infrapatellar fat pad cell concentrates containing mesenchymal stromal cells is safe and provides assistance in reducing pain and improving function in patients with knee cartilage lesions. Trial registration ChiCTR1800015379. Registered on 27 March 2018, http://www.chictr.org.cn/showproj.aspx?proj=25901.

Download Full-text

Some Special Aspects of Liver Repair after Resection and Administration of Multipotent Stromal Cells in Experiment

Life ◽

10.3390/life11010066 ◽

2021 ◽

Vol 11 (1) ◽

pp. 66

Author(s):

Igor Maiborodin ◽

Elena Lushnikova ◽

Marina Klinnikova ◽

Swetlana Klochkova

Keyword(s):

Bone Marrow ◽

Liver Resection ◽

Connective Tissue ◽

Light Microscopy ◽

Stromal Cells ◽

Multipotent Mesenchymal Stromal Cells ◽

Multipotent Stromal Cells ◽

Rapid Restoration ◽

Bone Marrow Origin

Changes in rat liver after resection and injection of autologous multipotent mesenchymal stromal cells of bone marrow origin (MSCs) transfected with the GFP gene and cell membranes stained with red-fluorescent lipophilic membrane dye were studied by light microscopy. It was found that after the introduction of MSCs into the damaged liver, their differentiation into any cells was not found. However, under the conditions of MSCs use, the number of neutrophils in the parenchyma normalizes earlier, and necrosis and hemorrhages disappear more quickly. It was concluded that the use of MSCs at liver resection for the rapid restoration of an organ is inappropriate, since the injected cells in vivo do not differentiate either into hepatocytes, into epithelial cells of bile capillaries, into endotheliocytes and pericytes of the vascular membranes, into fibroblasts of the scar or other connective tissue structures, or into any other cells present in the liver.

Download Full-text

The effects of co-transplantation of bone marrow hematopoietic stem cell and thymic multipotent stromal cells on the immune system of mice during its regeneration after cyclophosphamide treatment

Cell and Organ Transplantology ◽

10.22494/cot.v7i1.95 ◽

2019 ◽

Vol 7 (1) ◽

Author(s):

D. Demchenko ◽

I. Nikolskiy

Keyword(s):

Bone Marrow ◽

Immune System ◽

Lymph Nodes ◽

Stromal Cells ◽

Activity Level ◽

Delayed Type Hypersensitivity ◽

Blast Transformation ◽

Multipotent Stromal Cells ◽

Hematopoietic Stem ◽

Stimulation Of

The multipotent stromal cells (MSCs) are considered as one of the most promising agents for regenerating the immune system due to its powerful secretion of reparative factors and immunomodulatory properties.The purpose of the study is to investigate the effect of co-transplantation of bone marrow hematopoietic stem cells (HSCs) and thymic multipotent stromal cells (MSCs) on regeneration of murine immune system damaged by cyclophosphamide.Materials and methods. MSCs were obtained from thymuses of C57BL mice using explant technique. Bone marrow cells (BMCs) were obtained by flushing out the femur with nutrient medium. The immune deficiency of mice was modelled by the treatment with cyclophosphamide. After that, the cells were co-transplanted and the parameters of the immune system was evaluated. We determined the total number of erythrocytes, hematocrit, and hemoglobin concentration in peripheral blood; phases of the cell cycle and apoptosis of the cells of the mesenteric lymph nodes; the number of antibody-producing cells in the spleen; delayed type hypersensitivity (DTH); proliferative and cytotoxic activity of natural killer lymphocytes; phagocytic activity, level of spontaneous and induced bactericidal activity of peritoneal macrophages.Results. It was shown that in contrast to BMCs, the use of MSCs alone or co-transplantation of these cells increased the spontaneous proliferative activity of lymphocytes with a significant decrease in the number of lymph node cells in G0/G1 phase by 9.2 % and an increase in the number of lymphocytes in G2-M+S phase by 35 %, as well as restoring cellularity of bone marrow, thymus and lymph nodes in mice treated with cyclophosphamide. Regeneration of erythropoiesis was stimulated by BMCs, which was manifested by the normalization of hematocrit and hemoglobin, and an increase in the number of reticulocytes in the blood by 2.2 times compared with the group of mice receiving cyclophosphamide. Co-transplantation had less pronounced, but similar effect. Transplantation of thymic MSCs stimulated the natural cytotoxicity of splenocytes by 2.7 times and substantially increased the number of antibody-producing cells in the spleen by 1.7 times compared with the group of mice receiving cyclophosphamide. Co-transplantation had a pronounced suppressive effect on the blast transformation reaction induced by phytohemagglutinin by 1.7 times, but showed a stimulating effect on DTH response by 1.46 times. Transplantation of BMCs did not affect the functional activity of the immune system.Conclusion. The effects of co-transplantation of BMCs and thymic MSCs are realized in the several parts: stimulation of hematological parameters recovery (like under the effect of BMCs separately), normalization of cell number of lymphoid organs (as under the impact of thymic MSCs); inhibition of blast transformation activity and stimulation of DTH are the effects of co-transplantation.

Download Full-text