Stenting and cell technologies in the treatment of atherosclerotic renovascular hypertension Part 2. Effectiveness and safety of postnatal
Abstract
Aim. To assess effectiveness and safety of stem cell auto-transplantation (SCT) into renal and vertebral arteries among patients with renovascular hypertension (RVH) lasting over 10 years.
Material and methods. Seventy-eight patients were randomized into main (MG, n=26) and placebo groups (PG, n=52). Primary end-point was systolic blood pressure (SBP) level. Secondary end-points included: restenosis incidence; glomerular filtration rate (GFR); effective renal plasma flow (ERPF); creatinine level and microalbuminuria (MAU); quality of life (QoL); renal biopsy and immuno-hystochemical assay data; renal vessel calcification; cerebral metabolism level.
Results. Restenosis at 12 months was observed in 17% of both MG and CG patients; repeated revascularization was needed in 8%. Stenting resulted in average BP decrease from 181/107 to 142/93 mm Hg; after 6 weeks, no patient achieved target BP levels. After SCT into both renal arteries, BP normalization was achieved in 61% of MG participants. Only 23% of regenerated renal tissue originated from transplanted SC (trans-differentiation), the rest originated from local tissues (de-differentiation). After 50-55 weeks, in 37-39% of the patients Stage I AH was observed. At 6-8 weeks after SCT into both vertebral arteries, cerebral metabolism increased, and BP normalized, reducing from 138/90 to 119/69 mm Hg.
Conclusion. SCT plays an important role in renal artery thrombosis prevention and RVH control. Renal and vertebral artery SCT solves the problems of nephron destruction and renal tissue fibrosis, atherosclerosis treatment and harmful cerebral influences. Remaining problems include target organ damage and genetic defects.
About the Authors
Ya. L. GabinskyRussian Federation
M. S. Freydlina
Russian Federation
E. K. Bos
Netherlands
T. A. Naydanova
Russian Federation
S. D. Chernyshev
Russian Federation
B. V. Fadin
Russian Federation
References
1. Беленков Ю.Н., Агеев Ф.Т., Мареев В.Ю. и др. Мобилизация стволовых клеток костного мозга в лечении больных хронической сердечной недостаточностью. Кардиология 2003; 3: 12–6.
2. Беленков Ю.Н., Агеев Ф.Т., Мареев В.Ю. и др. Стволовые клетки и их применение для регенерации миокарда. Ж серднедостат 2003; 4: 168–73.
3. Владимирская Е.Б., Майорова О.А., Румянцев С.А. и др. Биологические основы и перспективы терапии стволовыми клетками. Москва “Медпрактика-М” 2005; 392 с.
4. Вермель А.Е. Стволовые клетки: общая характеристика и перспективы применения в клинической практике. Клин мед 2004; 1: 5–11.
5. Габбасов З.А., Соболева Э.Л. Стромальные стволовые клетки взрослого организма – резерв восстановительной хирургии. Клин геронт 2003; 5: 20–4.
6. Дыбан А.П. Стволовые клетки в экспериментальной и клинической медицине. Мед академ ж 2002; 3: 3–24.
7. Кобалава Ж.Д., Гудков К.М. Эволюция представлений о стресс-индуцированной артериальной гипертонии и применение антагонистов рецепторов ангиотензина II. Кардиоваск тер профил 2002; 2: 4–15.
8. Козлов К.Л. Интервенционная пластика венечных артерий. Санкт-Петербург “ЭЛБИ” 2000; 230 с.
9. Мушкамбаров Н.Н., Кузнецов С.Л. Молекулярная биология. Москва “ООО Мед информ агентство” 2003; 544 с.
10. Нефрология. Руководство для врачей. Под ред. И.Е. Тареевой. Москва “Медицина” 2000; 688 с.
11. Патофизиология заболеваний сердечно-сосудистой системы. Под ред. Л. Лилли; Пер. с англ. Москва “БИНОМ. Лаборатория знаний” 2003; 598 с.
12. Румянцев А.Г., Масчан А.А. Трансплантация гемопоэтических стволовых клеток у детей. Москва “МИА” 2003; 912 с.
13. Саркисов Д.С. Регенерация и ее клиническое значение. Москва “Медицина” 1979; 284 с.
14. Скворцова В.И. Артериальная гипертония и церебро-васкулярные нарушения. Сист гиперт 2005; 2: 9–12.
15. Титов В.Н. Клиническая биохимия и кардинальные вопросы патогенеза атеросклероза (обзор литературы). Клин лаб диагн 2000; 1: 3–9.
16. Титов В.Н. Патогенез атеросклероза для XXI века (обзор литературы). Клин лаб диагн 1998; 3–11.
17. Шахов В.П., Байков А.Н. Стволовые клетки. Реальность и перспективы. Современные аспекты биологии и медицины. Томск “СГУ” 2002; 110–2.
18. Шахов В.П., Попов С.В. Стволовые клетки и кардиомиогенез в норме и патологии. Томск “STT” 2004; 170 с.
19. Шулутко Б.И. Артериальная гипертензия 2000. Санкт-Петербург “РЕНКОР” 2001; 382 с.
20. Al-Awqati Q, and Oliver JA. Stem cells in the kidney. Kidney int 2002; 61: 387–95.
21. Ashish Bhalla, Sanjay D’Cruz, Lehl SS, et al. Renovascular hypertension – its evaluation and management. JIACM 2003; 4: 139–46.
22. Bianco P, Robey P. Mesenchymal Stem Cell: clinical applications J Clin Invest 2000; 105: 1663–8.
23. Chade AR, Rodriguez-Porcel M, Grande JP, et al. Mechanisms of renal structural alterations in combined hypercholesterolemia and renal artery stenosis. Arterioscler Thromb Vasc Biol 2003; 23: 1295–301.
24. Cogle CR, Yachnis AT, Laywell ED, et al. Bone marrow transdifferentiation in brain after transplantation: a retrospective study. Lancet 2004; 363(9419): 1432–7.
25. Essentials of stem cell biology / Edited by Robert Lanza. Elsevier Academic Press, US 2006; 312 p.
26. Lin F, Cordes K, Li L, et al. Hematopoietic stem cells contribute to the regeneration of renal tubules after renal ischemia-reperfusion injury in mice. J Am Soc Nephrol 2003; 14: 1188–99.
27. Haas S, Weidner N, Winkler J. Adult stem cell therapy in stroke. Curr Opin Neurol 2005; 18(1): 59–64.
28. Halme DG, Kessler DA. FDA regulation of stem-cell-based therapies. NEJM 2006; 355: 1730–5.
29. Duffield JS, Park KM, Hsiao Li-Li, et al. Restoration of tubular epithelial cells during repair of the postischemic kidney occurs independently of bone marrow-derivided stem cells. J Clin Invest 2005; 115: 1743–55.
30. Kuure S, Vuolteenaho R, Vainio S. Kidney morphogenesis: cellular and molecular regulation. Mech Dev 2000; 92: 31–45.
31. Lewis RA. Stem cell legacy: Leroy Stevens; The Scientists, A Stem Cell Legacy. The Scientist 2000; 14: 19–24.
32. Mezey Е, Key S, Vogelsang G, et al. Transplanted bone marrow generates new neurons in human brains. Proc Natl Acad Sci USA 2003; 100(3): 1364–9.
33. Okie S. Stem-cell politics. NEJM 2006; 355: 1633–5.
34. Okie S. Single-cell storm. NEJM 2006; 355: 1636–7.
35. Oliver JA, Barasch J, Yang J, et al. Metanephric mesenchyme contains embrionic renal stem cells. Am J Physiol Renal Physiol 2002; 283: 799–809.
36. Qiao J, Cohen D, Herzlinger D. The metanephric blastemal differentiates into collecting system and nephron epithelia in vitro. Development 1995; 121: 3207–14.
37. Safian RD, Textor SC. Renal-artery stenosis. N Engl J Med 2001; 6: 431–42.
38. Savitz SI, Dinsmore JH, Wechsler LR, et al. Cell Therapy for Stroke. Neurorx 2004; 1(4): 406–14.
39. Schwartz RS. The politics and promise of stem-cell research. NEJM 2006; 12: 1189–91.
40. Stark K, Vainio S, Vassileva G, et al. Epithelial transformation of metanephric mesenchyme in the developing kidney regulated by Wnt-4. Nature 1994; 372: 679–83.
41. Stem cells and the future of regenerative medicine. National Research Council. Institute of medicine. National Academy Press, Washington, DC, US. 2002, 47 p.
42. Kale S, Karihaloo A, Clark PR, et al. Bone marrow stem cells contribute to repaire of the ischemically injured renal tubule. J Clin Invest 2003; 112: 42–9.
Review
For citations:
Gabinsky Ya.L., Freydlina M.S., Bos E.K., Naydanova T.A., Chernyshev S.D., Fadin B.V. Stenting and cell technologies in the treatment of atherosclerotic renovascular hypertension Part 2. Effectiveness and safety of postnatal. Cardiovascular Therapy and Prevention. 2008;7(5):16-23. (In Russ.)