PERSPECTIVE APPROACHES FOR TREATMENT OF LOW-ENERGY INJURY BONE TISSUE INJURIES USING BIOENGINEERING METHODS AND CELL THERAPY
Introduction: Autologous mesenchymal stem cells (MSCs) are osteogenesis progenitor cells that activate the reparative processes in the zone of delayed fracture healing in osteoporosis and similar bone pathologies. Use of MSCs in regenerative medicine is one of the promising areas of scientific research. In this regard, in cooperation with Carnegie Mellon University (USA), an osteophilic bisphosphonate polymer capable of stably binding to MSC has been developed as a targeted transport platform. It has been previously shown that the polymer is able to inhibit osteoclastic activity in vitro, and, at the same time, it is not cytotoxic and does not affect the osteogenic differentiation of MSCs.
Goal: to perform preclinical studies of acute and chronic polymer toxicity, to assess the regenerative potential of local transplantation of MSCs functionalized with an osteophilic polymer in experimentally induced osteoporotic ulna fracture of small laboratory animals.
Methods: To confirm the therapeutic potential of MSCs functionalized with osteophilic polymer, in vivo studies were conducted on rats with the experimentally induced ulna fracture and experimental estrogen-dependent osteoporosis. Studies of acute and chronic toxicity of an osteophilic bisphosphonate polymer were carried out on the basis of the Republican State Pharmacopoeia Laboratory at the National Center for Expertise of Medicines, Medical Devices and Medical Equipment, Ministry of Health of the Republic of Kazakhstan
Results: Intravital analysis of the bone density dynamics in the zone of ulna fracture showed a statistically significant 27% increase in bone density 4 weeks after osteotomy of the ulna in the group of animals receiving 4 transplantations (once per week) of the MSC modified with the polymer. The results of intravital observations were confirmed by post-mortem analysis of histological slices of the fracture zone. A study of the dynamics of interstitial distribution of the MSCs showed the presence of transplanted cells in the area of the bone defect for at least one week after local injection of the modified cell. The results of preclinical biosafety studies have shown the absence of acute and chronic polymer toxicity.
Conclusion: The data obtained allowed us to conclude that the proposed combined approach, based on the use of cell therapy for MSCs modified with an osteophilic polymer, which has two functional groups - bisphosphonate and hydroxysuccimide, is a safe and an effective way to stimulate reparative osteogenesis in osteoporosis-associated traumatic bone injuries.
Yuliya I. Safarova (Yantsen)1, https://orcid.org/0000-0003-0695-0413
Farkhad S. Olzhayev1, https://orcid.org/0000-0002-1906-6654
Bauyrzhan A. Umbayev1, https://orcid.org/0000-0002-0286-7252
Akmaral S. Yerkebayeva2, https://orcid.org/0000-0002-0395-282X
Aisulu S. Karenkina3, https://orcid.org/0000-0002-0782-3099
Ivan V. Kotov3, https://orcid.org/0000-0003-0074-4520
Alan J. Russell4, https://orcid.org/0000-0001-5101-4371
Sholpan N. Askarova1*, https://orcid.org/0000-0001-6161-1671
1 National Laboratory Astana, Nazarbayev University, Nur-Sultan city, Republic of Kazakhstan;
2 School of Sciences and Humanities, Nazarbayev University, Nur-Sultan city, Republic of Kazakhstan;
3 GKP on PHV "Pathological Bureau" akimat Nur-Sultan city, Nur-Sultan city, Republic of Kazakhstan;
4 Institute for Complex Engineering, Carnegie Mellon University, Pittsburgh, USA
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Safarova (Yantsen) Yu.I., Olzhayev F.S., Umbayev B.A., Yerkebayeva A.S., Karenkina A.S., Kotov I.V., Russell A.J., Askarova Sh.N. Perspective approaches for treatment of low-energy injury bone tissue injuries using bioengineering methods and cell therapy // Nauka i Zdravookhranenie [Science & Healthcare]. 2019, (Vol.21) 5, pp. 68-80.Related publications:
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