MATIČNE ĆELIJE – OPŠTI PREGLED: OD RAZVOJNIH HEMOBIOLOŠKIH KONCEPATA DO (AUTO)GRAFTING-a U KLINIČKOJ PRAKSI

  • Bela Balint
  • Mirjana Pavlović Department of Computer and Electrical Engineering and Computer Science, Florida Atlantic University, Boca Raton, USA
  • Olivera Marković Department of Hematology with Oncohematology, Clinic of Internal Medicine, Clinical-Hospital Center "Bezanijska kosa", Belgrade, Serbia
  • Saša Borović
  • Milena Todorović Clinic for Hematology, University Clinical Center of Serbia, Belgrade, Serbia
DOI: https://doi.org/10.5937/smclk3-37014
Ključne reči: matične ćelije, plastičnost matičnih ćelija, transplantacija, regenerativna medicina

Sažetak


Konvencionalna transplantacija matičnih ćelija hematopoeze (MĆH) je dobro poznat metod lečenja brojnih stečenih i urođenih poremećaja hematopoeze, poremećaja imunskog sistema, kao i određenih metaboličkih oboljenja. Matične ćelije (MĆ) se mogu definisati kao ćelije koje imaju sposobnost samoobnavljanja i koje poseduju visoki proliferativni kapacitet, kao i potencijal da se diferentuju u funkcionalno kompetentne zrele ćelije. MĆ se mogu podeliti na embrionalne MĆ (EMĆ) i tkivno operdeljene, odnosno adultne MĆ – kao
što su one iz kostne srži, periferne krvi i iz krvi pupčane vrpce, kao i druge ne-hematopoetske odnosno somatske ćelije. Kod odraslih, MĆ se obično smatraju ograničenim po pitanju njihovog regenerativnog potencijala i potencijala diferentovanja, dok su EMĆ „prave“ totipotentne/pluripotentne ćelije, jer imaju sposobnost da se razviju i u endoderm, ektoderm i mezoderm – tj. u sva tri tipa embrionalnog tkiva u ljudskom organizmu. Među MĆ koje se potencijalno mogu presaditi, ove ćelije predstavljaju vrstu koja najviše obećava, ali i koja je i najkontroverznija. Manje zrele ili primitivnije MĆH imaju potencijal da se diferentuju,
ne samo u sve vrste ćelija krvi, već i u neke vrste somatskih ćelija (plastičnost MĆ). U različitim kliničkim uslovima, transplantacija nezrelih (primitivnih) MĆ dovodi do repopulacije kostne srži primaoca transplantata, uz kasniju potpunu, stabilnu i dugoročnu rekonstituciju hematopoeze. Imajući u vidu da su primitivne ćelije takođe sposobne za ukalemljenje (homing) u različita tkiva, autologna implantacija MĆ u oštećeno i/ili ishemično područje indukuje njihovo naseljavanje i sledstveno transdiferentovanje u ćelijske linije organa
domaćina, uključujući i neovaskularizaciju. Stoga su one klinički primenljive u oblasti regenerativne medicine, u lečenju tkivnih oštećenja miokarda, mozga, krvnih sudova, jetre, pankreasa i drugih tkiva. Svrha ovog pregleda jeste rekapitulacija ključnih otkrića u oblasti istraživanja MĆ, koja je u fazi ubrzanog razvoja. U radu je dat i pregled primene MĆ u tzv. konvencionalnim transplantacijama i u regenerativnoj medicini. Uz to, dat je i sažet kritički osvrt na naša sopstvena istraživanja u oblasti MĆ.

Reference


  1. Apperly J, Carreras E, Gluckman E, Gratwohl A, Maszi T. Hameatopoietic Stem Cell Transplantation. The EBMT Handbook, 5th Paris: ESH; 2008..

  2. Pavlovic M, Balint B. Stem cells and tissue engineering. New York: Springer; 2013.

  3. Pavlovic M, Balint B. Bioengineering and cancer stem cell concept. New York: Springer; 2015.

  4. Balint B, Obradovic S, Todorovic M, Pavlovic M, Mihaljevic B. Stem cell-based (auto)grafting: from innovative research toward clinical use in regenerative medicine. In: Alimoghaddam K, editor. Stem Cell Biology in Normal Life and Diseases. London: InTechOpen. 2013. p. 111–35.

  5. Balint B, Vucetić D, Ostojić G, Ljubenov M. Osnovi transfuziologije sa hemobiologijom. Beograd: Medicinski fakultet VMA – Medija centar Odbrana; 2015.

  6. Blau HM, Brazelton TR, Weimann JM. The evolving concept of a stem cell: entity or function? Cell. 2001; 105(7): 829–41.

  7. Smith A. A glossary for stem-cell biology. Nature 2006; 441: 1060.

  8. D'Souza A, Fretham C, Lee SJ, Arora M, Brunner J, Chhabra S, et al. Current Use of and Trends in Hematopoietic Cell Transplantation in the United States. Biol Blood Marrow Transplant 2020; 26(8): e177–e182.

  9. Kanate AS, Majhail NS, Savani BN, Bredeson C, Champlin RE, Crawford S, et al. Indications for Hematopoietic Cell Transplantation and Immune Effector Cell Therapy: Guidelines from the American Society for Transplantation and Cellular Therapy. Biol Blood Marrow Transplant. 2020; 26(7): 1247–56.

  10. Balint B, Ivanovic Z, Petakov M, Taseski J, Jovcic G, Stojanovic N, et al. The cryopreservation protocol optimal for progenitor recovery is not optimal for preservation of MRA. Bone Marrow Transpl 1999; 23: 613–9.

  11. Balint B, Pavlovic M, Todorovic M. Stem cells: Hemobiology and clinical data summarizing: a critical review. Scr Med 2020; 51(4): 61-71.

  12. Balint B, Pavlovic M, Todorovic M. From nucleated to ex vivo manipulated stem cells – an updated biological and clinical synopsis. Medical Word 2020; 1(1): 1–

  13. Balint B, Todorovic M, Ostojic G, Ljubenov M, Dusan Vucetic, Aleksandar Jevtic et al. Hematopoietic stem cells – from hemobiology to the extracorporeal manipulative viewpoints. Anest Reanim Transf 2017; 43(1–2): 9–22.

  14. Balint B, Stamatovic D, Todorovic M, Jevtic M, Ostojic G, Pavlovic M, et al. Stem cells in the arrangement of bone marrow repopulation and regenerative medicine. Vojnosanit Pregl 2007; 64(7): 481–4.

  15. Balint B, Kanjuh V, Todorovic-Balint M,Petkovic S, Balint V, Pavlovic M. Stem cell harvesting and ex vivo manipulations. Bilt Transfuziol 2015; 61 (1–2): 37–42.

  16. Ivanovic Z, Petakov M, Jovcic G, Biljanovic–Paunovic L, Balint B, Milenkovic P. Pluripotent and committed haematopoietic progenitor cells in rat. Comp Haematol Int 1997; 7: 1–6.

  17. Skoric D, Balint B, Petakov M, Sindjic M, Rodic P. Collection strategies and cryopreservation of umbilical cord blood. Transfusion Medicine 2007; 17(2): 107–13.

  18. Balint B, Stamatovic D, Todorovic M, Elez M, Vojvodic D, Pavlovic M, Cucuz–Jokic M. Autologous transplant in aplastic anemia: quantity of CD34+/CD90+ subset as the predictor of clinical outcome. Transf Apher Sci 2011; 45: 137–41.

  19. Balint B, Stanojevic I, Todorovic M, Stamatovic D, Pavlovic M, Vojvodic D. Relative frequency of immature CD34+/CD90+ subset in peripheral blood following mobilization correlates narrowly and inversely with the absolute count of harvested stem cells in multiple myeloma patients. Vojnosanit Pregl 2017; 74(11): 1071–7.

  20. Todorovic Balint M, Jelicic J, Bila J, Balint B, Antic D, Trajkovic G , et al. Influence of applied CD34+ cell dose on the survival of Hodgkin's lymphoma and multiple myeloma patients following autologous stem cell transplants. Vojnosanit Pregl 2020; 77(8): 844–51.

  21. Balint B, Ljubenov M, Stamatovic D, Todorovic M, Pavlovic M, Ostojic G, et al. Stem cell harvesting protocol research in autologous transplantation setting: large volume vs. conventional cytapheresis Vojnosanit Pregl 2008; 65(7): 545–51.

  22. Savic A, Balint B, Urosevic I, Rajic N, Todorovic M, Percic I Popovic S. Syngeneic peripheral blood stem cell transplantation with immunosuppression for hepatitis–associated severe aplastic anemia. Turkish J Hematology 2010; 27(4): 294–8.

  23. Obradovic S, Balint B, Romanovic R, Trifunovic Z, Rusovic S, Baskot B, et al. Influence of intracoronary injections of bone-marrow-derived mononuclear cells on large myocardial infarction outcome: quantum of initial necrosis is the key. Vojnosanit Pregl 2009; 66(12): 998–1004.

  24. Obradovic S, Balint B, Trifunovic Z. Stem cell therapy in myocardial infarction clinical point of view and the results of the REANIMA Study (REgenerAtion of Myocardium with boNe Marrow Mononuclear Cells in MyocArdial Infarction). In: Gholamrezanezhad A, editor. Stem cells in clinic and research. London: InTechOpen. 2011. p. 233–58.

  25. Trifunovic Z, Obradovic Z, Balint B, Ilic R, Vukic Z, Sisic M et al.. Ischemic cardiomyopathy treated with coronary bypass surgery and concomitant intramyocardial bone marrow mononuclear cell implantation – long term follow-up study. Vojnosanit Pregl 2015; 72(3): 225–32.

  26. Ratajzcak MZ, Kucia M, Reca R, Majka M et al, Stem cell plasticity revised: CXR4 positive cells expressing mRNA for earlu muscle, liver and neural cells “hide out” in the bone marrow. Leukemia 2004; 19(1): 29–40.

  27. Kucia M, Wojakowski W, Ryan R, Machalinski B, Gozdzik J, Majka M, Baran J, Ratajczak J, and Ratjczak MZ. The migration of bone marrow–derived non–hematopoietic tissue–commited stem cells is regulated in and SDF-1-, HGF-, and LIF dependent manner. Arch Immunol Ther Exp 2006, 54, 2: 121–135

  28. Kucia M, Reca R, Campbell FR, Surma–Zuba E, Majka M, Ratajczak M, and Ratajczak MZ A population of very small embryonic – like (VSEL) CXR4+SSEA–1+Oct4+ stem cells identified in adult bone marrow. Leukemia 2006, 20: 857–69

  29. Shin DM, Zuba-Surma EK, Wu W, Ratajczak J, Wysoczynski M, Ratajczak MZ, et al. Novel epigenetic mechanisms that control pluripotency and quiescence of adult bone marrow-derived Oct4(+) very small embryonic-like stem cells. Leukemia. 2009; 23(11): 2042–51.

  30. Ratajczak MZ, Ratajczak J, Kucia M. Very small embryonic-like stem cells (VSELs). Circ Res 2019; 124(2): 208–10.

  31. Wojakowski W, Kucia M, Zuba-Surma E, Jadczyk T, Książek B, Ratajczak MZ, et al. Very small embryonic-like stem cells in cardiovascular repair. Pharmacol Ther 2011; 129(1): 21–8.

  32. Zuba-Surma EK, Wu W, Ratajczak J, Kucia M, Ratajczak MZ. Very small embryonic-like stem cells in adult tissues-potential implications for aging. Mech Ageing Dev 2009; 130(1–2): 58–66.

  33. Bhartiya D, Singh P, Sharma D, Kaushik A. Very small embryonic-like stem cells (VSELs) regenerate whereas mesenchymal stromal cells (MSCs) rejuvenate diseased reproductive tissues. Stem Cell Rev Rep 2021 Aug 19. doi: 10.1007/s12015-021-10243-6.

  34. Wen C, Xie L, Hu C. Roles of mesenchymal stem cells and exosomes in interstitial cystitis/bladder pain syndrome. J Cell Mol Med 2022; 26(3): 624–635.

  35. Rodríguez-Fuentes DE, Fernández-Garza LE, Samia-Meza JA, Barrera-Barrera SA, Caplan AI, Barrera-Saldaña HA. Mesenchymal stem cells current clinical applications: A systematic review. Arch Med Res 2021; 52(1): 93–101.

  36. Todorovic V, Markovic D, Milosevic–Jovcic N, Petakov M, Balint B, Colic M et al. Dental pulp stem cells – potential significance in regenerative medicine. Stom Glas S 2008; 55: 170–9.

  37. Jo H, Brito S, Kwak BM, Park S, Lee MG, Bin BH. Applications of mesenchymal stem cells in skin regeneration and rejuvenation. Int J Mol Sci 2021; 22(5): 2410. doi: 10.3390/ijms22052410.

  38. Zhou T, Yuan Z, Weng J, Pei D, Du X, He C, Lai P. Challenges and advances in clinical applications of mesenchymal stromal cells. J Hematol Oncol 2021; 14(1): 24. doi: 10.1186/s13045-021-01037-x.

  39. Colman A. Profile of John Gurdon and Shinya Yamanaka, 2012 Nobel laureates in medicine or physiology. Proc Natl Acad Sci USA. 2013; 110(15): 5740–1.

  40. Xu ZL, Huang XJ. Haploidentical stem cell transplantation for aplastic anemia: the current advances and future challenges. Bone Marrow Transplant 2021; 56(4): 779–85.

  41. Gulbas Z. Haploidentical stem cell transplantation-bone marrow vs peripheral blood. Transfus Apher Sci 2018; 57(2): 168–170.

  42. Petakov M, Balint B, Bugarski D, Jovčić G, Stojanović N, Vojvodić D et al. Donor leukocyte infusion – the effect of mutual reactivity of donor´s and recipietnt´s peripheral blood mononuclear cell on hematopoietic progenitor cells growth. Vojnosanit Pregl 2000; 57 (5 Suppl): 89–93.

  43. Balint B, Kanjuh V, Ostojić M, Obradović S, Todorović M, Rafajlovski S. Matične ćelije – biologija i primena u regenerativnoj medicini kod bolesti srca. In: Ostojić M, Kanjuh V, Nedeljković S, editors. Kardiologija. Beograd: Medicinski fakultet; 2011.

  44. Balint B. Stem cells – unselected or selected, unfrozen or cryopreserved: marrow repopulation capacity and plasticity potential in experimental and clinical settings. Mac Med Rewiev 2004; 58 (Suppl 63): 22–4.

  45. Balint B, Todorovic M, Pavlovic M. Stem cells – hemobiological events and clinical applications. Mac Med Rewiev 2019; 73(Supl 106): 19–22.

Objavljeno
2022/06/29
Broj časopisa
Vol. 3 Br. 2 (2022): Srpski medicinski časopis Lekarske komore
Rubrika
Po izboru urednika