endosergЭндокринная хирургияEndocrine Surgery2306-35132310-3965Типография «Печатных дел Мастер»10.14341/serg12773endoserg-12773Research ArticleОБЗОРREVIEWПрименение стволовых клеток в терапии синдрома диабетической стопы: анализ клинических данных (обзор литературы)The use of stem cells in the treatment of diabetic foot syndrome: analysis of clinical data (review)https://orcid.org/0000-0001-5980-5549БатраеваА. И.BatraevaA. I.

Батраева Алия Ильдаровна.

450008, Уфа, Ленина, д.3

Aliya I. Batraeva.

450008, Ufa, Lenin st., 3

medicalscience@bk.ruhttps://orcid.org/0000-0002-3718-9877БурляеваВ. В.BurlyaevaV. V.

Бурляева Валерия Викторовна.

Москва

Valeriya V. Burlyaeva.

Moscow

vers1488@yandex.ruhttps://orcid.org/0000-0003-0417-7818МудрикИ. В.MudrikI. V.

Мудрик Иван Вячеславович.

Уфа

Ivan V. Mudrik.

Ufa

i.mudrik@mail.ruhttps://orcid.org/0000-0002-7123-8572СинакаеваС. С.SinakaevaS. S.

Синакаева Сабина Саматовна.

Уфа

Sabina S. Sinakaeva.

Ufa

Ssinakaeva@gmail.comhttps://orcid.org/0000-0003-3474-4924ДегтяреваД. И.DegtyarevaD. I.

Дегтярева Дарья Игоревна.

Москва

Darya I. Degtyareva.

Moscow

dasha00mailru@mail.ruhttps://orcid.org/0000-0001-5751-2398СалимовВ. В.SalimovV. V.

Салимов Вадим Валерьевич.

Уфа

Vadim V. Salimov.

Ufa

vadim.salimov_official@mail.ruБашкирский государственный медицинский университетРоссияBashkir state medical universityRussian FederationМосковский государственный медико-стоматологический университет им. А.И. ЕвдокимоваРоссияA.I. Evdokimov Moscow State Medical and Dental UniversityRussian Federation202504062025191512Copyright © Батраева А.И., Бурляева В.В., Мудрик И.В., Синакаева С.С., Дегтярева Д.И., Салимов В.В., 20252025Батраева А.И., Бурляева В.В., Мудрик И.В., Синакаева С.С., Дегтярева Д.И., Салимов В.В.Batraeva A.I., Burlyaeva V.V., Mudrik I.V., Sinakaeva S.S., Degtyareva D.I., Salimov V.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.surg-endojournals.ru/jour/article/view/12773

Синдром диабетической стопы (СДС) является одним из наиболее распространенных осложнений сахарного диабета (СД) и является следствием патологических изменений периферической нервной системы, микроциркуляторного русла, а также костно-суставного аппарата стопы, что представляет угрозу развития язвенно-некротических процессов и гангрены. Сообщается, что примерно у 15% пациентов с СД развивается СДС, из них от 14 до 24% подвергаются ампутации конечностей. Также СДС вносит значительный вклад в раннюю смертность, поскольку 68% людей с ампутированными конечностями умирают в течение 5 лет. Авторы провели электронный поиск публикаций в базах данных PubMed и Elibrary. Клеточная терапия использовалась в качестве адъювантной терапии при лечении СДС. Результаты, представленные в настоящем исследовании, демонстрируют, что применение мезенхимальных стволовых клеток безопасно и эффективно без клинически значимых побочных эффектов и, следовательно, может помочь предотвратить высокие ампутации конечностей при неосложненных язвах диабетической стопы. Однако по-прежнему существует ряд проблем с согласованием наиболее применимого типа клеток, способа их введения и дозировок, что требует проведения дальнейших исследований.

Diabetic foot syndrome (DFS) is one of the most common complications of diabetes and is a consequence of pathological changes in the peripheral nervous system, microcirculatory bed, as well as the osteoarticular apparatus of the foot, which poses a threat to the development of ulcerative necrotic processes and gangrene. It is reported that approximately 15% of patients with DM develop SDS, of which 14 to 24% undergo limb amputation. SDS also contributes significantly to early mortality, as 68% of amputees die within 5 years. The authors conducted an electronic search for publications in the PubMed and Elibrary databases. Stem cell therapy has been used as adjuvant therapy in the treatment of SDS. The results presented in this study demonstrate that the use of mesenchymal stem cells is safe and effective without clinically significant side effects and, therefore, can help prevent high limb amputations in uncomplicated diabetic foot ulcers. However, there are still a number of problems with the coordination of the most applicable type of cells, the method of their administration and dosages, which requires further research.

сахарный диабетсиндром диабетической стопыстволовые клеткиязвы стопытерапияdiabetes mellitusdiabetic foot syndromestem cellsfoot ulcerstherapyReferencesДедов И.И., Шестакова М.В., Викулова О.К., Железнякова А.В., Исаков М.А., Сазонова Д.В., Мокрышева Н.Г. Сахарный диабет в Российской Федерации: динамика эпидемиологических показателей по данным Федерального регистра сахарного диабета за период 2010 – 2022 гг. // Сахарный диабет. — 2023. — Т.26. — №2. — С.104-123. doi: https://doi.org/10.14341/DM13035Dedov II, Shestakova MV, Vikulova OK, Zheleznyakova AV, Isakov MA, Sazonova DV, Mokrysheva NG. Diabetes mellitus in the Russian Federation: dynamics of epidemiological indicators according to the Federal Register of Diabetes Mellitus for the period 2010–2022. Diabetes mellitus. 2023;26(2):104-123. (In Russ.) doi: https://doi.org/10.14341/DM13035Бардюгов П.С., Паршиков М. В. Деформации стоп у пациентов с синдромом диабетической стопы (обзор литературы). // Гений ортопедии. — 2022. — Т. 28. — №3. — С. 452-458.Bordyugov PS, Parshikov MV. Deformities of the feet in patients with diabetic foot syndrome (literature review). Genij ortopedii. 2022;28(3):452-458 (In Russ.)Levy N, Gillibrand W. Management of diabetic foot ulcers in the community: an update. Br J Community Nurs. 2019;24(3):14-19. doi: https://doi.org/10.12968/bjcn.2019.24.Sup3.S14Levy N, Gillibrand W. Management of diabetic foot ulcers in the community: an update. Br J Community Nurs. 2019;24(3):14-19. doi: https://doi.org/10.12968/bjcn.2019.24.Sup3.S14Nascimento de Aquino MJ, Caetano de Souza AC, Pereira Borges JW, da Silva Negreiros FD, de Sousa Gonçalves M, Oliveira Martins PM, Magalhães Moreira TM. Prevalence, Incidence and Factors Associated with Diabetic Foot in People with Type 2 Diabetes: Systematic Review with Meta-Analysis. Curr Diabetes Rev. 2023. doi: https://doi.org/10.2174/1573399819666230407093450Nascimento de Aquino MJ, Caetano de Souza AC, Pereira Borges JW, da Silva Negreiros FD, de Sousa Gonçalves M, Oliveira Martins PM, Magalhães Moreira TM. Prevalence, Incidence and Factors Associated with Diabetic Foot in People with Type 2 Diabetes: Systematic Review with Meta-Analysis. Curr Diabetes Rev. 2023. doi: https://doi.org/10.2174/1573399819666230407093450Коцлова А.А., Власов Т.Д., Давыденко В.В. Влияние клеточной и генной терапии на заживление трофических язв у пациентов с нейроишемической формой синдрома диабетической стопы. // Хирургическая практика. — 2016. — №2. — С.32-38.Kozlova AA, Vlasov TD, Davydenko VV. Influence of cell and gene therapy on the healing of trophic ulcers in patients with neuroischemic form of diabetic foot syndrome. Surgical practice. 2016;(2):32-38 (In Russ.)Макаров С.В., Муселимян Н.Х. Вклад регенеративной медицины в терапию аутоиммунных заболеваний нервной системы. // Гены и Клетки. — 2022. — Т.17. — №3. — С. 141-142.Makarov SV, Muselimyan NH. Contribution of regenerative medicine to the therapy of autoimmune diseases of the nervous system. Genes & Cells. 2022;17(3):141-142. (In Russ.)Shu X, Shu S, Tang S, Yang L, Liu D, Li K, et al. Efficiency of stem cell based therapy in the treatment of diabetic foot ulcer: a meta-analysis. Endocr J. 2018;65(4):403-413. doi: https://doi.org/10.1507/endocrj.EJ17-0424.Shu X, Shu S, Tang S, Yang L, Liu D, Li K, et al. Efficiency of stem cell based therapy in the treatment of diabetic foot ulcer: a meta-analysis. Endocr J. 2018;65(4):403-413. doi: https://doi.org/10.1507/endocrj.EJ17-0424.Калинин РЕ, Сучков ИА, Мжаванадзе НД, Крылов АА, Исаев АА, Плакса ИЛ, Деев РВ. Регенеративные технологии в лечении синдрома диабетической стопы. Гены и Клетки. 2017;12(1):15-26. doi: https://doi.org/10.23868/gc120634Kalinin RE, Suchkov IA, Mzhavanadze ND, Krylov AA, Isaev AA, Plaksa IL, Deev RV. Regenerative technologies in treatment of diabetic foot ulcers. Genes & Cells. 2017;12(1):15-26. (In Russ.) doi: https://doi.org/10.23868/gc120634Люндуп А.В., Максимова Н.В., Мельниченко Г.А., Помыткин И.А., Клабуков И.Д. Аутологичные мезенхимальные стволовые клетки как эффективный активатор эпителизации при синдроме диабетической стопы. // Гены и Клетки. — 2017. — Т.12. — №3. — С.150-151. doi: https://doi.org/10.23868/gc121002Lyundup AV, Maksimova NV, Mel’nichenko GA, Pomytkin IA, Klabukov ID. Autologichnye mezenkhimal’nye stvolovye kletki kak effektivnyy aktivator epitelizatsii pri sindrome diabeticheskoy stopy. Genes & Cells. 2017;12(3):150-151 (In Russ.). doi: https://doi.org/10.23868/gc121002Yu Q, Qiao GH, Wang M, Yu L, Sun Y, Shi H, Ma TL. Stem Cell-Based Therapy for Diabetic Foot Ulcers. Front Cell Dev Biol. 2022;10:812262. doi: https://doi.org/10.3389/fcell.2022.812262Yu Q, Qiao GH, Wang M, Yu L, Sun Y, Shi H, Ma TL. Stem Cell-Based Therapy for Diabetic Foot Ulcers. Front Cell Dev Biol. 2022;10:812262. doi: https://doi.org/10.3389/fcell.2022.812262Huang P, Li S, Han M, Xiao Z, Yang R, Han ZC. Autologous transplantation of granulocyte colony-stimulating factor-mobilized peripheral blood mononuclear cells improves critical limb ischemia in diabetes. Diabetes Care. 2005;28(9):2155-2160. doi: https://doi.org/10.2337/diacare.28.9.2155Huang P, Li S, Han M, Xiao Z, Yang R, Han ZC. Autologous transplantation of granulocyte colony-stimulating factor-mobilized peripheral blood mononuclear cells improves critical limb ischemia in diabetes. Diabetes Care. 2005;28(9):2155-2160. doi: https://doi.org/10.2337/diacare.28.9.2155Procházka V, Gumulec J, Jalůvka F, Salounová D, Jonszta T, et al. Cell therapy, a new standard in management of chronic critical limb ischemia and foot ulcer. Cell Transplant. 2010;19(11):1413-1424. doi: https://doi.org/10.3727/096368910X514170Procházka V, Gumulec J, Jalůvka F, Salounová D, Jonszta T, et al. Cell therapy, a new standard in management of chronic critical limb ischemia and foot ulcer. Cell Transplant. 2010;19(11):1413-1424. doi: https://doi.org/10.3727/096368910X514170Dash NR, Dash SN, Routray P, Mohapatra S, Mohapatra PC. Targeting nonhealing ulcers of lower extremity in human through autologous bone marrow-derived mesenchymal stem cells. Rejuvenation Res. 2009;12(5):359-366. doi: https://doi.org/10.1089/rej.2009.0872Dash NR, Dash SN, Routray P, Mohapatra S, Mohapatra PC. Targeting nonhealing ulcers of lower extremity in human through autologous bone marrow-derived mesenchymal stem cells. Rejuvenation Res. 2009;12(5):359-366. doi: https://doi.org/10.1089/rej.2009.0872Jain P, Perakath B, Jesudason MR, Nayak S. The effect of autologous bone marrow-derived cells on healing chronic lower extremity wounds: results of a randomized controlled study. Ostomy Wound Manage. 2011;57(7):38-44Jain P, Perakath B, Jesudason MR, Nayak S. The effect of autologous bone marrow-derived cells on healing chronic lower extremity wounds: results of a randomized controlled study. Ostomy Wound Manage. 2011;57(7):38-44Maksimova N, Krasheninnikov M, Zhang Y, Ponomarev E, Pomytkin I, et al. Early passage autologous mesenchymal stromal cells accelerate diabetic wound re-epithelialization: A clinical case study. Cytotherapy. 2017;19(12):1548-1550 doi: https://doi.org/10.1016/j.jcyt.2017.08.017Maksimova N, Krasheninnikov M, Zhang Y, Ponomarev E, Pomytkin I, et al. Early passage autologous mesenchymal stromal cells accelerate diabetic wound re-epithelialization: A clinical case study. Cytotherapy. 2017;19(12):1548-1550 doi: https://doi.org/10.1016/j.jcyt.2017.08.017Maksimova NV, Michenko AV, Krasilnikova OA, et al. Mesenchymal stromal cells therapy alone does not lead to the complete restoration of the skin parameters in diabetic foot patients within a 3-year follow-up period. BioImpacts. September 2021. doi: https://doi.org/10.34172/bi.2021.22167Maksimova NV, Michenko AV, Krasilnikova OA, et al. Mesenchymal stromal cells therapy alone does not lead to the complete restoration of the skin parameters in diabetic foot patients within a 3-year follow-up period. BioImpacts. September 2021. doi: https://doi.org/10.34172/bi.2021.22167Ганина А.М., Аскаров М.Б. Применение мезенхимальных стволовых клеток при лечении сахарного диабета 1 типа и его осложнений. // Universum: медицина и фармакология. — 2022.— Т.4. — №87. — С.4-6Ganina AM, Askarov MB. The use of mesenchymal stem cells in the treatment of type 1 diabetes mellitus and its complications. Universum: Medicine and Pharmacology. 2022;4(87):4-6. (In Russ.)Lu D, Chen B, Liang Z, Deng W, Jiang Y, Li S, Xu J, Wu Q, Zhang Z, Xie B, Chen S. Comparison of bone marrow mesenchymal stem cells with bone marrow-derived mononuclear cells for treatment of diabetic critical limb ischemia and foot ulcer: a double-blind, randomized, controlled trial. Diabetes Res Clin Pract. 2011;92(1):26-36. doi: https://doi.org/10.1016/j.diabres.2010.12.010Lu D, Chen B, Liang Z, Deng W, Jiang Y, Li S, Xu J, Wu Q, Zhang Z, Xie B, Chen S. Comparison of bone marrow mesenchymal stem cells with bone marrow-derived mononuclear cells for treatment of diabetic critical limb ischemia and foot ulcer: a double-blind, randomized, controlled trial. Diabetes Res Clin Pract. 2011;92(1):26-36. doi: https://doi.org/10.1016/j.diabres.2010.12.010Kirana S, Stratmann B, Prante C, Prohaska W, Koerperich H, et al. Autologous stem cell therapy in the treatment of limb ischaemia induced chronic tissue ulcers of diabetic foot patients. Int J Clin Pract. 2012;66(4):384-393. doi: https://doi.org/10.1111/j.1742-1241.2011.02886.xKirana S, Stratmann B, Prante C, Prohaska W, Koerperich H, et al. Autologous stem cell therapy in the treatment of limb ischaemia induced chronic tissue ulcers of diabetic foot patients. Int J Clin Pract. 2012;66(4):384-393. doi: https://doi.org/10.1111/j.1742-1241.2011.02886.xMoon KC, Suh HS, Kim KB, Han SK, Young KW, Lee JW, Kim MH. Potential of Allogeneic Adipose-Derived Stem Cell-Hydrogel Complex for Treating Diabetic Foot Ulcers. Diabetes. 2019;68(4):837-846. doi: https://doi.org/10.2337/db18-0699Moon KC, Suh HS, Kim KB, Han SK, Young KW, Lee JW, Kim MH. Potential of Allogeneic Adipose-Derived Stem Cell-Hydrogel Complex for Treating Diabetic Foot Ulcers. Diabetes. 2019;68(4):837-846. doi: https://doi.org/10.2337/db18-0699Uzun E, Güney A, Gönen ZB, Özkul Y, Kafadar İH, Günay M, Mutlu M. Intralesional allogeneic adipose-derived stem cells application in chronic diabetic foot ulcer: Phase I/2 safety study. Foot Ankle Surg. 2021;27(6):636-642. doi: https://doi.org/10.1016/j.fas.2020.08.002Uzun E, Güney A, Gönen ZB, Özkul Y, Kafadar İH, Günay M, Mutlu M. Intralesional allogeneic adipose-derived stem cells application in chronic diabetic foot ulcer: Phase I/2 safety study. Foot Ankle Surg. 2021;27(6):636-642. doi: https://doi.org/10.1016/j.fas.2020.08.002Han SK, Kim HR, Kim WK. The treatment of diabetic foot ulcers with uncultured, processed lipoaspirate cells: a pilot study. Wound Repair Regen. 2010;18(4):342-348. doi: https://doi.org/10.1111/j.1524-475X.2010.00593.xHan SK, Kim HR, Kim WK. The treatment of diabetic foot ulcers with uncultured, processed lipoaspirate cells: a pilot study. Wound Repair Regen. 2010;18(4):342-348. doi: https://doi.org/10.1111/j.1524-475X.2010.00593.xRai V, Moellmer R, Agrawal DK. Stem Cells and Angiogenesis: Implications and Limitations in Enhancing Chronic Diabetic Foot Ulcer Healing. Cells. 2022;11(15):2287. doi: https://doi.org/10.3390/cells11152287Rai V, Moellmer R, Agrawal DK. Stem Cells and Angiogenesis: Implications and Limitations in Enhancing Chronic Diabetic Foot Ulcer Healing. Cells. 2022;11(15):2287. doi: https://doi.org/10.3390/cells11152287Nalisa DL, Moneruzzaman M, Changwe GJ, Mobet Y, Li LP, Ma YJ, Jiang HW. Stem Cell Therapy for Diabetic Foot Ulcers: Theory and Practice. J Diabetes Res. 2022;2022:6028743. doi: https://doi.org/10.1155/2022/6028743Nalisa DL, Moneruzzaman M, Changwe GJ, Mobet Y, Li LP, Ma YJ, Jiang HW. Stem Cell Therapy for Diabetic Foot Ulcers: Theory and Practice. J Diabetes Res. 2022;2022:6028743. doi: https://doi.org/10.1155/2022/6028743Liu R, Dong R, Chang M, Liang X, Wang HC. Adipose-Derived Stem Cells for the Treatment of Diabetic Wound: From Basic Study to Clinical Application. Front Endocrinol (Lausanne). 2022;13:882469. doi: https://doi.org/10.3389/fendo.2022.882469Liu R, Dong R, Chang M, Liang X, Wang HC. Adipose-Derived Stem Cells for the Treatment of Diabetic Wound: From Basic Study to Clinical Application. Front Endocrinol (Lausanne). 2022;13:882469. doi: https://doi.org/10.3389/fendo.2022.882469Weiss ARR, Dahlke MH. Immunomodulation by Mesenchymal Stem Cells (MSCs): Mechanisms of Action of Living, Apoptotic, and Dead MSCs. Front Immunol. 2019;10:1191. doi: https://doi.org/10.3389/fimmu.2019.01191Weiss ARR, Dahlke MH. Immunomodulation by Mesenchymal Stem Cells (MSCs): Mechanisms of Action of Living, Apoptotic, and Dead MSCs. Front Immunol. 2019;10:1191. doi: https://doi.org/10.3389/fimmu.2019.01191Guillamat-Prats R. The Role of MSC in Wound Healing, Scarring and Regeneration. Cells. 2021;10(7):1729. doi: https://doi.org/10.3390/cells10071729Guillamat-Prats R. The Role of MSC in Wound Healing, Scarring and Regeneration. Cells. 2021;10(7):1729. doi: https://doi.org/10.3390/cells10071729

The authors declare that there are no conflicts of interest present.