KA Vetoshkin, NV Isaeva, MA Butolina, NV Minaeva, NA Zorina, MN Khorobrykh, YuS Zmeeva
Kirov Research Institute of Hematology and Transfusiology, 72 Krasnoarmeiskaya str., Kirov, Russian Federation, 610027
For correspondence: Konstantin Aleksandrovich Vetoshkin, MD, PhD, 72 Krasnoarmeiskaya str., Kirov, Russian Federation, 610027; Tel.: +7(905)870-06-92; e-mail: kostyavetoshkin@yandex.ru
For citation: Vetoshkin KA, Isaeva NV, Butolina MA, et al. Aldehyde Dehydrogenase as a Marker of Early Mesenchymal Progenitor Cells in Donor Bone Marrow Stroma. Clinical oncohematology. 2020;13(2):123–8 (In Russ).
DOI: 10.21320/2500-2139-2020-13-2-123-128
ABSTRACT
Aim. To analyze the growth rate of mesenchymal stromal cell (MSC) culture depending on the aldehyde dehydrogenase-positive (ALDH+) cell count.
Materials & Methods. The study involved bone marrow mesenchymal cell cultures of 10 donors (5 men and 5 women) with median age of 34.5 years (range 14–38 years). Nucleated cells were obtained by density gradient centrifugation. MSCs were cultivated according to the conventional protocol using platelet-rich donor plasma. Stromal cell identification and ALDH+ cell counting were performed by laser flow cytometry according to the criteria of the International Society for Cell Therapy.
Results. The growth rate of MSC cultures and ALDH+ cell counts are maximum at primary and passage No. 1, becoming significantly lower by passage No. 3. The relationship between MSC culture growth rate and ALDH+ cell count was revealed. The older the donor, the lower MSC culture growth rate and ALDH+ cell count in bone marrow stroma.
Conclusion. The data obtained indicate the relationship between bone marrow MSC culture growth rate, donor’s age, and ALDH+ cell count. ALDH-expressing cells proved to confer MSC population renewal. Based on the results acquired, we assume that the studied ALDH marker can serve as an objective criterion for placing mesenchymal cell elements into the category of early progenitor cells.
Keywords: cell culture, mesenchymal cells, aldehyde dehydrogenase, culture growth rate.
Received: November 28, 2019
Accepted: March 1, 2020
REFERENCES
-
Осипова Е.Ю., Никитина В.А., Астрелина Т.А. и др. Динамика скорости роста, иммунофенотипа и генетическая стабильность мезенхимальных стволовых клеток костного мозга человека на ранних и поздних пассажах при культивировании ex vivo. Онкогематология. 2009;4(1):44–50.
[Osipova EYu, Nikitina VA, Astrelina TA, et al. Human bone marrow mesenchymal stem cell growth rate dynamics, immunophenotype and genetic stability on early and late passages at ex vivo culturing. 2009;4(1):44–50. (In Russ)]
-
Пулин А.А., Сабурина И.Н., Репин В.С. Поверхностные маркеры, характеризующие мультипотентные мезенхимальные стромальные клетки (ММСК) костного мозга человека. Клеточная трансплантология и тканевая инженерия. 2008;3(3):25–30. [Pulin AA, Saburina IN, Repin VS. Surface markers of human bone marrow multipotent mesenchymal stromal cells (MMSC). Kletochnaya transplantologiya i tkanevaya inzheneriya. 2008;3(3):25–30. (In Russ)]
-
Harichandan A, Sivasubramaniyan K, Buhring H-J. Prospective isolation and characterization of human bone marrow-derived MSCs. Advances in biochemical engineering and biotechnology. 2013;129:1–17. doi: 10.1007/10_2012_147.
-
Бигильдеев А.Е. Устройство и регуляция отдела стволовых мезенхимных клеток: Дис. … д-ра биол. наук. М., 2017.
[Bigildeev AE. Ustroistvo i regulyatsiya otdela stvolovykh mezenkhimnykh kletok. (Structure and regulation of mesenchymal stem cells.) [dissertation] Moscow; 2017. (In Russ)]
-
Шипунова И.Н. Иерархическая структура стромального микроокружения кроветворной ткани в норме и при заболеваниях системы крови: Автореф. дис. … д-ра биол. наук. М., 2018.
[Shipunova IN. Ierarkhicheskaya struktura stromalnogo mikrookruzheniya krovetvornoi tkani v norme i pri zabolevaniyakh sistemy krovi. (Hierarchical structure of stromal microenvironment of hematopoietic tissue in norm and disorder of blood system.) [dissertation] Moscow; 2018. (In Russ)]
-
Gordon MY, Goldman JM, Gordon-Smith EC. 4-hydroperoxycyclophosphamide inhibits proliferation by human granulocyte-macrophage colony-forming cells (GM-CFC) but spares more primitive progenitor cells. Leuk Res. 1985;9(8):1017–21. doi: 10.1016/0145-2126(85)90072-4.
-
Sahovic EA, Colvin M, Hilton J, Ogawa M. Role of aldehyde dehydrogenase in survival of progenitors for murine blast cell colonies after treatment with 4-hydroperoxycyclophosphamide in vitro. Cancer Res. 1988;48(5):1223–6.
-
Moreb JS, Turner C, Sreerama L, et al. Interleukin-1 and tumor necrosis factor alpha induce class 1 aldehyde dehydrogenase mRNA and protein in bone marrow cells. Leuk Lymphoma. 1995;20(1–2):77–84. doi: 10.3109/10428199509054756.
-
Gentry T, Foster S, Winstead L, et al. Simultaneous isolation of human BM hematopoietic, endothelial and mesenchymal progenitor cells by flow sorting based on aldehyde dehydrogenase activity: implications for cell therapy. Cytotherapy. 2007;9(3):259–74. doi: 10.1080/14653240701218516.
-
Storms RW, Trujillo AP, Springer JB, et al. Isolation of primitive human hematopoietic progenitors on the basis of aldehyde dehydrogenase activity. Proc Nat Acad Sci USA. 1999;96(16):9118–23. doi: 10.1073/pnas.96.16.9118.
-
Fallon P, Gentry T, Balber AE, et al. Mobilized peripheral blood SSCloALDHbrcells have the phenotipic and functional properties of primitive haemotopoietic cells and their number correlates with engraftment following autologous transplantation. Br J Haematol. 2003;122(1):99–108. doi: 10.1046/j.1365-2141.2003.04357.x.
-
Hess DA, Meyerrose TE, Wirthlin L, et al. Functional characterization of highly purified human hematopoietic repopulating cells isolated according to aldehyde dehydrogenase activity. Blood. 2004;104(6):1648–55. doi: 10.1182/blood-2004-02-0448.
-
Najar M, Crompot E, van Grunsven LA, et al. Aldehyde dehydrogenase activity in adipose tissue: isolation and gene expression profile of distinct sub-population of mesenchymal stromal cells. Stem Cell Rev Rep. 2018;14(4):599–611. doi: 10.1007/s12015-017-9777-6.
-
Najar M, Crompot E, van Grunsven LA, et al. Aldehyde dehydrogenase activity of Wharton jelly mesenchymal stromal cells: isolation and characterization. Cytotechnology. 2019;71(1):427–41. doi: 10.1007/s10616-018-0283-8.
-
Najar M, Crompot E, van Grunsven LA, et al. Foreskin-derived mesenchymal stromal cells with aldehyde dehydrogenase activity: isolation and gene profiling. BMC Cell Biol. 2018;19(1):4. doi: 10.1186/s12860-018-0157-0.
-
Lange C, Cakiroglu F, Spiess A, et al. Accelerated and Safe Expansion of Human Mesenchymal Stromal Cells in Animal Serum-Free Medium for Transplantation and Regenerative Medicine. J Cell Physiol. 2007;213(1):18–26. doi: 10.1002/jcp.21081.
-
Astori G, Amati E, Bambi F, et al. Platelet lysate as a substitute for animal serum for ex-vivo expansion of mesenchymal stem/stromal cells: present and future. Stem Cell Res Ther. 2016;7(1):93. doi: 10.1186/s13287-016-0352-x.
-
Sorokina T, Shipounova I, Bigildeev A, et al. Alterations of the bone marrow stromal microenvironment in adult patients with leukemia before and after the treatment. 2016;128(22):2668. doi: 10.1182/blood.v128.22.2668.2668.
-
Шипунова И.Н., Петинати Н.А., Сац Н.В. и др. Стромальные клетки-предшественники при остром лимфобластном лейкозе. Гематология и трансфузиология. 2014;59(S1):31.
[Shipunova IN, Petinati NA, Sats NV, et al. Stromal progenitor cells in acute lymphoblastic leukemia. Gematologiya i transfuziologiya. 2014;59(S1):31. (In Russ)]
-
Супотницкий М.В., Елапов А.А., Меркулов В.А. и др. Основные технологические процессы, используемые при производстве биомедицинских клеточных продуктов. Биопрепараты. 2015;2:36–45.
[Supotnitskii MV, Elapov AA, Merkulov VA, et al. Common technological processes used in manufacture of biomedical cell culture products. Biopreparaty. 2015;2:36–45. (In Russ)]
-
Reya T, Mottison SJ, Clarke MF, Weissman IL. Stem cells, cancer and cancer stem cells. Nature. 2001;414(6859):105–11. doi: 10.1038/35102167.
-
Hess DA, Wirthlin L, Craft TP, et al. Selection based on CD133 and high aldehyde dehydrogenase activity isolates long-term reconstituting human hematopoietic stem cells. Blood. 2006;107(5):2162–9. doi: 10.1182/blood-2005-06-2284.
-
Corti S, Locatelli F, Papadimitriou D, et al. Identification of a primitive brain-derived neural stem cell population based on aldehyde dehydrogenase activity. Stem Cells. 2006;24(4):975–85. doi: 10.1634/stemcells.2005-0217.
-
Sladek NE. Human aldehyde dehydrogenases: potential pathological, pharmacological, and toxicological impact. J Biochem Mol Toxicol. 2003;17(1):7–23. doi: 10.1002/jbt.10057.
-
Chute JP, Muramoto GG, Whitesides J, et al. Inhibition of aldehyde dehydrogenase and retinoid signaling induces the expansion of human hematopoietic stem cells. Proc Nat Acad Sci USA. 2006;103(31):11707–12. doi: 10.1073/pnas.0603806103.
-
Muramoto GG, Russell JL, Safi R, et al. Inhibition of aldehyde dehydrogenase expands hematopoietic stem cells with radioprotective capacity. Stem Cells. 2010;28(3):523–34. doi: 10.1002/stem.299.
-
Sladek Aldehyde dehydrogenase-mediated cellular relative insensitivity to the oxazaphosphorines. Curr Pharm Des. 1999;5(8):607–25.
-
Caplan The mesengenic process. Clin Plast Surg. 1994;21(3):429–35.
-
Gnecchi M, Melo LG. Bone marrow-derived mesenchymal stem cells: isolation, expansion, characterization, viral transduction, and production of conditioned medium. Meth Mol Biol. 2009;482:281–94. doi: 10.1007/978-1-59745-060-7_18.
-
Wexler SA, Donaldson C, Denning-Kendall P, et al. Adult bone marrow is a rich source of human mesenchymal ‘stem’ cells but umbilical cord and mobilized adult blood are not. Br J Haematol. 2003;121(2):368–74. doi: 10.1046/j.1365-2141.2003.04284.x.