Research Article
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Determination of mTOR activity depending on donor age of mesenchymal stem cells isolated from adipose tissue

Year 2023, Volume: 16 Issue: 4, 704 - 714, 01.10.2023

Hayriye Sarıkaya Elif Önder Nazlı Çil Ergun Mete Gülçin Abban Mete

https://doi.org/10.31362/patd.1337120

Abstract

Purpose: Aging in living organisms is an inevitable physiological consequence. Cellular senescence occurs not
only in cells that have completed their differentiation, but also in stem cells. Mammalian target of Rapamycin
protein complex (mTOR) has an important role in cell growth and metabolism. The mTOR, which plays an
important role in cell proliferation, also regulates cellular aging and directs the bioenergetic infrastructure. The
aim of the study is to determine the mTOR expression of mesenchymal stem cell (MSC) obtained from adipose
tissue depending on the donor age.
Materials and methods: Six-week-old pubertal rats were named Group 1 (n=6), 10-12-week-old reproductive
period rats were named Group 2 (n=6), and 20-month-old rats were named Group 3 (n=6). The isolation of MSC
was performed by primary explant culture method from adipose tissue taken from groups. Characterization and
differentiation experiments were performed in MSC obtained. The activity of mTOR (mTORC1 and mTORC2)
in MSC was determined by qRT-PCR method. Caspase 3, 8, 9, Bax and Bcl-2 expressions were evaluated by
Real-time polymerase chain reaction (qRT-PCR) method.
Results: In our study, it was determined that the highest expression of apoptotic markers was in Group 1 and
the lowest expression was in Group 2. When mTOR expression was evaluated, mTORC1 was found to be
highest in Group 2 and lowest in Group 1. mTORC2 expression in Group 1 was lower than in other groups.
Although the expression of mTORC1 and mTORC2 in Group 3 was not as high as in Group 2, it was statistically
significant (p<0.05).
Conclusion: In this study, we found that both mTORC1 and mTORC2 are differentially expressed in stem cells
depending on donor age. Further studies are needed to better understand the functional consequences of this
difference.

Keywords

Aging adipose tissue mTOR mesenchymal stem cells

Supporting Institution

This work was supported by The Pamukkale University Scientific Research Projects Coordination Unit

Project Number

Project number: 2021SABE003

Thanks

Thanks to The Pamukkale University Scientific Research Projects Coordination Unit for their supports.

References

  • 1. Matic I, Antunovic M, Brkic S, et al. Expression of OCT-4 and SOX-2 in Bone Marrow-Derived Human Mesenchymal Stem Cells during Osteogenic Differentiation. Open Access Maced J Med Sci 2016;4:9-16. https://doi.org/10.3889/oamjms.2016.008
  • 2. Alves H, Munoz Najar U, De Wit J, et al. A link between the accumulation of DNA damage and loss of multi-potency of human mesenchymal stromal cells. J Cell Mol Med 2010;14:2729-2738. https://doi.org/10.1111/j.1582-4934.2009.00931.x
  • 3. Jang YY, Sharkis SJ. A low level of reactive oxygen species selects for primitive hematopoietic stem cells that may reside in the low-oxygenic niche. Blood 2007;110:3056-3063. https://doi.org/10.1182/blood-2007-05-087759 4. López Otín C, Blasco MA, Partridge L, Serrano M, Kroemer G. The hallmarks of aging. Cell 2013;153:1194-1217. https://doi.org/10.1016/j.cell.2013.05.039
  • 5. Lees H, Walters H, Cox LS. Animal and human models to understand ageing. Maturitas 2016;93:18-27. https://doi.org/10.1016/j.maturitas.2016.06.008
  • 6. Durmaz C, Şen E. Kök hücrelerde DNA hasarı ve onarımı. Tıp Fakültesi Klinikleri Dergisi 2022;5:19-26. https://doi.org/10.17932/IAU.TFK.2018.008/tfk_v05i1003
  • 7. Bengal E, Perdiguero E, Serrano AL, Muñoz Cánoves P. Rejuvenating stem cells to restore muscle regeneration in aging. F1000Res 2017;6:76. https://doi.org/10.12688/f1000research.9846.1
  • 8. Rossi DJ, Bryder D, Zahn JM, et al. Cell intrinsic alterations underlie hematopoietic stem cell aging. Proc Natl Acad Sci USA 2005;102:9194-9199. https://doi.org/10.1073/pnas.0503280102
  • 9. Morrison SJ, Wandycz AM, Akashi K, Globerson A, Weissman IL. The aging of hematopoietic stem cells. Nat Med 1996;2:1011-1016. https://doi.org/10.1038/nm0996-1011
  • 10. Sudo K, Ema H, Morita Y, Nakauchi H. Age-associated characteristics of murine hematopoietic stem cells. J Exp Med 2000;192:1273-1280. https://doi.org/10.1084/jem.192.9.1273
  • 11. Biteau B, Hochmuth CE, Jasper H. JNK activity in somatic stem cells causes loss of tissue homeostasis in the aging Drosophila gut. Cell Stem Cell 2008;3:442-455. https://doi.org/10.1016/j.stem.2008.07.024
  • 12. Nakada D, Oguro H, Levi BP, et al. Oestrogen increases haematopoietic stem-cell self-renewal in females and during pregnancy. Nature 2014;505:555-558. https://doi.org/10.1038/nature12932
  • 13. Ün B, Ferah MA, Ün BÇ. Mezenkimal kök hücre ve koşullandırılmış besiyerinin ovaryum hasarı üzerindeki tedavi edici etkileri. SDÜ Tıp Fakültesi Dergisi 2021;28:179-185 https://doi.org/10.17343/sdutfd.654926
  • 14. Igarashi M, Guarente L. mTORC1 and sırt1 cooperate to foster expansion of gut adult stem cells during calorie restriction. Cell 2016;166:436-450. https://doi.org/10.1016/j.cell.2016.05.044
  • 15. Zhou S, Zilberman Y, Wassermann K, Bain SD, Sadovsky Y, Gazit D. Estrogen modulates estrogen receptor alpha and beta expression, osteogenic activity, and apoptosis in mesenchymal stem cells (MSCs) of osteoporotic mice. J Cell Biochem Suppl 2001;36:144-155 https://doi.org/10.1002/jcb.1096
  • 16. Brinckmann M, Kaschina E, Altarche Xifró W, et al. Estrogen receptor alpha supports cardiomyocytes indirectly through post-infarct cardiac c-kit+ cells. J Mol Cell Cardiol 2009;47:66-75. https://doi.org/10.1016/j.yjmcc.2009.03.014
  • 17. Oh WJ, Jacinto E. mTOR complex 2 signaling and functions. Cell Cycle 2011;10:2305-2316. https://doi.org/10.4161/cc.10.14.16586
  • 18. Tee AR, Manning BD, Roux PP, Cantley LC, Blenis J. Tuberous sclerosis complex gene products, Tuberin and Hamartin, control mTOR signaling by acting as a GTPase-activating protein complex toward Rheb. Curr Biol 2003;13:1259-1268. https://doi.org/10.1016/s0960-9822(03)00506-2
  • 19. Martin SK, Fitter S, Dutta AK, et al. Brief report: the differential roles of mTORC1 and mTORC2 in mesenchymal stem cell differentiation. Stem Cells 2015;33:1359-1365. https://doi.org/10.1002/stem.1931
  • 20. Kim E, Goraksha Hicks P, Li L, Neufeld TP, Guan KL. Regulation of TORC1 by Rag GTPases in nutrient response. Nat Cell Biol 2008;10:935-945. https://doi.org/10.1038/ncb1753
  • 21. Phinney DG, Prockop DJ. Concise review: mesenchymal stem/multipotent stromal cells: the state of transdifferentiation and modes of tissue repair--current views. Stem Cells 2007;25:2896-2902. https://doi.org/10.1634/stemcells.2007-0637
  • 22. Bell A, Gagnon A, Grunder L, Parikh SJ, Smith TJ, Sorisky A. Functional TSH receptor in human abdominal preadipocytes and orbital fibroblasts. Am J Physiol Cell Physiol 2000;279:335-340. https://doi.org/10.1152/ajpcell.2000.279.2.C335
  • 23. Cho HJ, Park J, Lee HW, Lee YS, Kim JB. Regulation of adipocyte differentiation and insulin action with rapamycin. Biochem Biophys Res Commun 2004;321:942-948. https://doi.org/10.1016/j.bbrc.2004.07.050
  • 24. El Chaar D, A. Gagnon, and A. Sorisky. Inhibition of insulin signaling and adipogenesis by rapamycin: effect on phosphorylation of p70 S6 kinase vs eIF4E-BP1. Int J Obes Metab Disord 2004;28:191-198. https://doi.org/10.1038/sj.ijo.0802554
  • 25. Zhang HH, Huang J, Düvel K, et al. Insulin stimulates adipogenesis through the Akt-TSC2-mTORC1 pathway. PLoS One 2009;47:6189. https://doi.org/10.1371/journal.pone.0006189
  • 26. Isomoto S, Hattori K, Ohgushi H, Nakajima H, Tanaka Y, Takakura Y. Rapamycin as an inhibitor of osteogenic differentiation in bone marrow-derived mesenchymal stem cells. J Orthop Sci 2007;121:83-88. https://doi.org/10.1007/s00776-006-1079-9
  • 27. Lee KW, Yook JY, Son MY, et al. Rapamycin promotes the osteoblastic differentiation of human embryonic stem cells by blocking the mTOR pathway and stimulating the BMP/Smad pathway. Stem Cells Dev 2010;19:557-568. https://doi.org/10.1089/scd.2009.0147
  • 28. Bitto A, Ito TK, Pineda VV, et al. Transient rapamycin treatment can increase lifespan and healthspan in middle-aged mice. Elife 2016;5:16351. https://doi.org/10.7554/eLife.16351
  • 29. Chen C, Liu Y, Liu Y, Zheng P. mTOR regulation and therapeutic rejuvenation of aging hematopoietic stem cells. Sci Signal 2009;298:75. https://doi.org/10.1126/scisignal.2000559
  • 30. Johnson SC, Rabinovitch PS, Kaeberlein M. mTOR is a key modulator of ageing and age-related disease. Nature 2013;493:338-345. https://doi.org/10.1038/nature11861
  • 31. Ylmaz ÖH, Katajisto P, Lamming DW, et al. mTORC1 in the Paneth cell niche couples intestinal stem-cell function to calorie intake. Nature. 2012;486:490-495. https://doi.org/10.1038/nature11163
  • 32. Igarashi M, Guarente L. mTORC1 and SIRT1 cooperate to foster expansion of gut adult stem cells during calorie restriction. Cell 2016;166:436-450. https://doi.org/10.1016/j.cell.2016.05.044
  • 33. Weichhart T, Hengstschläger M, Linke M. Regulation of innate immune cell function by mTOR. Nat Rev Immunol 2015;15:599-614. https://doi.org/10.1038/nri3901
  • 34. Sukhbaatar N, Hengstschläger M, Weichhart T. mTOR-mediated regulation of dendritic cell differentiation and function. Trends Immunol 2016;37:778-789. https://doi.org/10.1016/j.it.2016.08.009
  • 35. Araki K, Ellebedy AH, Ahmed R. TOR in the immune system. Curr Opin Cell Biol 2011;236:707-715. https://doi.org/10.1016/j.ceb.2011.08.006
  • 36. Ogawa T, Tokuda M, Tomizawa K, et al. Osteoblastic differentiation is enhanced by rapamycin in rat osteoblast-like osteosarcoma (ROS 17/2.8) cells. Biochem Biophys Res Commun 1998;249:226-230. https://doi.org/10.1006/bbrc.1998.9118

Adipoz dokudan izole edilen mezenkimal kök hücrelerin donör yaşına bağlı olarak mTOR aktivitesinin belirlenmesi

Year 2023, Volume: 16 Issue: 4, 704 - 714, 01.10.2023

Hayriye Sarıkaya Elif Önder Nazlı Çil Ergun Mete Gülçin Abban Mete

https://doi.org/10.31362/patd.1337120

Abstract

Amaç: Canlı organizmalarda yaşlanma kaçınılmaz bir fizyolojik sonuçtur. Hücresel yaşlanma sadece
farklılaşmasını tamamlamış hücrelerde değil, kök hücrelerde de meydana gelir. Rapamisin protein kompleksinin
memeli hedefi (mTOR), hücre büyümesinde ve metabolizmasında önemli bir role sahiptir. Hücre çoğalmasında
önemli rol oynayan mTOR, aynı zamanda hücresel yaşlanmayı düzenler ve biyoenerjetik altyapıyı yönlendirir.
Çalışmanın amacı, donör yaşına bağlı olarak yağ dokusundan elde edilen mezenkimal kök hücrelerin (MSC)
mTOR ekspresyonunu belirlemektir.
Gereç ve yöntem: Altı haftalık pubertal sıçanlar Grup 1 (n=6), 10-12 haftalık reprodüktif dönem sıçanları Grup 2
(n=6) ve 20 aylık sıçanlar Grup 3 (n=6) olarak isimlendirildi. Gruplardan alınan yağ dokusundan primer eksplant
kültür metodu ile MSC izolasyonu yapıldı. Elde edilen MSC'de karakterizasyon ve farklılaşma deneyleri yapıldı.
Kök hücrelerdeki mTOR aktivitesi (mTORC1 ve mTORC2) qRT-PCR yöntemi ile belirlendi. Caspase 3, 8, 9, Bax
ve Bcl-2 ekspresyonları Real-time polymerase chain reaction (qRT-PCR) yöntemi ile değerlendirildi.
Bulgular: Çalışmamızda apoptotik belirteçlerin en yüksek ekspresyonunun Grup 1'de, en düşük ekspresyonun
Grup 2'de olduğu belirlendi. mTOR ekspresyonu değerlendirildiğinde, mTORC1 en yüksek Grup 2'de, en düşük
Grup 1'de bulundu. Grup 1'deki mTORC2 ifadesi diğer gruplara göre daha düşüktü. Grup 3'teki mTORC1 ve
mTORC2 ekspresyonu Grup 2'deki kadar yüksek olmasa da istatistiksel olarak anlamlıydı (p<0.05).
Sonuç: Bu çalışmada hem mTORC1 hem de mTORC2'nin donör yaşına bağlı olarak kök hücrelerde farklı
şekilde eksprese edildiğini bulduk. Bu farkın fonksiyonel sonuçlarını daha iyi anlamak için daha fazla çalışmaya
ihtiyaç vardır.

Keywords

Yaşlanma yağ doku mTOR mezenkimal kök hücreler

Project Number

Project number: 2021SABE003

References

  • 1. Matic I, Antunovic M, Brkic S, et al. Expression of OCT-4 and SOX-2 in Bone Marrow-Derived Human Mesenchymal Stem Cells during Osteogenic Differentiation. Open Access Maced J Med Sci 2016;4:9-16. https://doi.org/10.3889/oamjms.2016.008
  • 2. Alves H, Munoz Najar U, De Wit J, et al. A link between the accumulation of DNA damage and loss of multi-potency of human mesenchymal stromal cells. J Cell Mol Med 2010;14:2729-2738. https://doi.org/10.1111/j.1582-4934.2009.00931.x
  • 3. Jang YY, Sharkis SJ. A low level of reactive oxygen species selects for primitive hematopoietic stem cells that may reside in the low-oxygenic niche. Blood 2007;110:3056-3063. https://doi.org/10.1182/blood-2007-05-087759 4. López Otín C, Blasco MA, Partridge L, Serrano M, Kroemer G. The hallmarks of aging. Cell 2013;153:1194-1217. https://doi.org/10.1016/j.cell.2013.05.039
  • 5. Lees H, Walters H, Cox LS. Animal and human models to understand ageing. Maturitas 2016;93:18-27. https://doi.org/10.1016/j.maturitas.2016.06.008
  • 6. Durmaz C, Şen E. Kök hücrelerde DNA hasarı ve onarımı. Tıp Fakültesi Klinikleri Dergisi 2022;5:19-26. https://doi.org/10.17932/IAU.TFK.2018.008/tfk_v05i1003
  • 7. Bengal E, Perdiguero E, Serrano AL, Muñoz Cánoves P. Rejuvenating stem cells to restore muscle regeneration in aging. F1000Res 2017;6:76. https://doi.org/10.12688/f1000research.9846.1
  • 8. Rossi DJ, Bryder D, Zahn JM, et al. Cell intrinsic alterations underlie hematopoietic stem cell aging. Proc Natl Acad Sci USA 2005;102:9194-9199. https://doi.org/10.1073/pnas.0503280102
  • 9. Morrison SJ, Wandycz AM, Akashi K, Globerson A, Weissman IL. The aging of hematopoietic stem cells. Nat Med 1996;2:1011-1016. https://doi.org/10.1038/nm0996-1011
  • 10. Sudo K, Ema H, Morita Y, Nakauchi H. Age-associated characteristics of murine hematopoietic stem cells. J Exp Med 2000;192:1273-1280. https://doi.org/10.1084/jem.192.9.1273
  • 11. Biteau B, Hochmuth CE, Jasper H. JNK activity in somatic stem cells causes loss of tissue homeostasis in the aging Drosophila gut. Cell Stem Cell 2008;3:442-455. https://doi.org/10.1016/j.stem.2008.07.024
  • 12. Nakada D, Oguro H, Levi BP, et al. Oestrogen increases haematopoietic stem-cell self-renewal in females and during pregnancy. Nature 2014;505:555-558. https://doi.org/10.1038/nature12932
  • 13. Ün B, Ferah MA, Ün BÇ. Mezenkimal kök hücre ve koşullandırılmış besiyerinin ovaryum hasarı üzerindeki tedavi edici etkileri. SDÜ Tıp Fakültesi Dergisi 2021;28:179-185 https://doi.org/10.17343/sdutfd.654926
  • 14. Igarashi M, Guarente L. mTORC1 and sırt1 cooperate to foster expansion of gut adult stem cells during calorie restriction. Cell 2016;166:436-450. https://doi.org/10.1016/j.cell.2016.05.044
  • 15. Zhou S, Zilberman Y, Wassermann K, Bain SD, Sadovsky Y, Gazit D. Estrogen modulates estrogen receptor alpha and beta expression, osteogenic activity, and apoptosis in mesenchymal stem cells (MSCs) of osteoporotic mice. J Cell Biochem Suppl 2001;36:144-155 https://doi.org/10.1002/jcb.1096
  • 16. Brinckmann M, Kaschina E, Altarche Xifró W, et al. Estrogen receptor alpha supports cardiomyocytes indirectly through post-infarct cardiac c-kit+ cells. J Mol Cell Cardiol 2009;47:66-75. https://doi.org/10.1016/j.yjmcc.2009.03.014
  • 17. Oh WJ, Jacinto E. mTOR complex 2 signaling and functions. Cell Cycle 2011;10:2305-2316. https://doi.org/10.4161/cc.10.14.16586
  • 18. Tee AR, Manning BD, Roux PP, Cantley LC, Blenis J. Tuberous sclerosis complex gene products, Tuberin and Hamartin, control mTOR signaling by acting as a GTPase-activating protein complex toward Rheb. Curr Biol 2003;13:1259-1268. https://doi.org/10.1016/s0960-9822(03)00506-2
  • 19. Martin SK, Fitter S, Dutta AK, et al. Brief report: the differential roles of mTORC1 and mTORC2 in mesenchymal stem cell differentiation. Stem Cells 2015;33:1359-1365. https://doi.org/10.1002/stem.1931
  • 20. Kim E, Goraksha Hicks P, Li L, Neufeld TP, Guan KL. Regulation of TORC1 by Rag GTPases in nutrient response. Nat Cell Biol 2008;10:935-945. https://doi.org/10.1038/ncb1753
  • 21. Phinney DG, Prockop DJ. Concise review: mesenchymal stem/multipotent stromal cells: the state of transdifferentiation and modes of tissue repair--current views. Stem Cells 2007;25:2896-2902. https://doi.org/10.1634/stemcells.2007-0637
  • 22. Bell A, Gagnon A, Grunder L, Parikh SJ, Smith TJ, Sorisky A. Functional TSH receptor in human abdominal preadipocytes and orbital fibroblasts. Am J Physiol Cell Physiol 2000;279:335-340. https://doi.org/10.1152/ajpcell.2000.279.2.C335
  • 23. Cho HJ, Park J, Lee HW, Lee YS, Kim JB. Regulation of adipocyte differentiation and insulin action with rapamycin. Biochem Biophys Res Commun 2004;321:942-948. https://doi.org/10.1016/j.bbrc.2004.07.050
  • 24. El Chaar D, A. Gagnon, and A. Sorisky. Inhibition of insulin signaling and adipogenesis by rapamycin: effect on phosphorylation of p70 S6 kinase vs eIF4E-BP1. Int J Obes Metab Disord 2004;28:191-198. https://doi.org/10.1038/sj.ijo.0802554
  • 25. Zhang HH, Huang J, Düvel K, et al. Insulin stimulates adipogenesis through the Akt-TSC2-mTORC1 pathway. PLoS One 2009;47:6189. https://doi.org/10.1371/journal.pone.0006189
  • 26. Isomoto S, Hattori K, Ohgushi H, Nakajima H, Tanaka Y, Takakura Y. Rapamycin as an inhibitor of osteogenic differentiation in bone marrow-derived mesenchymal stem cells. J Orthop Sci 2007;121:83-88. https://doi.org/10.1007/s00776-006-1079-9
  • 27. Lee KW, Yook JY, Son MY, et al. Rapamycin promotes the osteoblastic differentiation of human embryonic stem cells by blocking the mTOR pathway and stimulating the BMP/Smad pathway. Stem Cells Dev 2010;19:557-568. https://doi.org/10.1089/scd.2009.0147
  • 28. Bitto A, Ito TK, Pineda VV, et al. Transient rapamycin treatment can increase lifespan and healthspan in middle-aged mice. Elife 2016;5:16351. https://doi.org/10.7554/eLife.16351
  • 29. Chen C, Liu Y, Liu Y, Zheng P. mTOR regulation and therapeutic rejuvenation of aging hematopoietic stem cells. Sci Signal 2009;298:75. https://doi.org/10.1126/scisignal.2000559
  • 30. Johnson SC, Rabinovitch PS, Kaeberlein M. mTOR is a key modulator of ageing and age-related disease. Nature 2013;493:338-345. https://doi.org/10.1038/nature11861
  • 31. Ylmaz ÖH, Katajisto P, Lamming DW, et al. mTORC1 in the Paneth cell niche couples intestinal stem-cell function to calorie intake. Nature. 2012;486:490-495. https://doi.org/10.1038/nature11163
  • 32. Igarashi M, Guarente L. mTORC1 and SIRT1 cooperate to foster expansion of gut adult stem cells during calorie restriction. Cell 2016;166:436-450. https://doi.org/10.1016/j.cell.2016.05.044
  • 33. Weichhart T, Hengstschläger M, Linke M. Regulation of innate immune cell function by mTOR. Nat Rev Immunol 2015;15:599-614. https://doi.org/10.1038/nri3901
  • 34. Sukhbaatar N, Hengstschläger M, Weichhart T. mTOR-mediated regulation of dendritic cell differentiation and function. Trends Immunol 2016;37:778-789. https://doi.org/10.1016/j.it.2016.08.009
  • 35. Araki K, Ellebedy AH, Ahmed R. TOR in the immune system. Curr Opin Cell Biol 2011;236:707-715. https://doi.org/10.1016/j.ceb.2011.08.006
  • 36. Ogawa T, Tokuda M, Tomizawa K, et al. Osteoblastic differentiation is enhanced by rapamycin in rat osteoblast-like osteosarcoma (ROS 17/2.8) cells. Biochem Biophys Res Commun 1998;249:226-230. https://doi.org/10.1006/bbrc.1998.9118
There are 35 citations in total.

Details

Primary Language English
Subjects Biochemistry and Cell Biology (Other), Pathology
Journal Section Research Article
Authors

Hayriye Sarıkaya 0009-0002-3276-3208

Elif Önder 0000-0002-7187-1669

Nazlı Çil 0000-0002-2164-8688

Ergun Mete 0000-0002-0854-2440

Gülçin Abban Mete 0000-0001-6794-3685

Project Number Project number: 2021SABE003
Early Pub Date September 20, 2023
Publication Date October 1, 2023
Submission Date August 4, 2023
Acceptance Date September 20, 2023
Published in Issue Year 2023 Volume: 16 Issue: 4

Cite

APA Sarıkaya, H., Önder, E., Çil, N., Mete, E., et al. (2023). Determination of mTOR activity depending on donor age of mesenchymal stem cells isolated from adipose tissue. Pamukkale Medical Journal, 16(4), 704-714. https://doi.org/10.31362/patd.1337120
AMA Sarıkaya H, Önder E, Çil N, Mete E, Abban Mete G. Determination of mTOR activity depending on donor age of mesenchymal stem cells isolated from adipose tissue. Pam Med J. October 2023;16(4):704-714. doi:10.31362/patd.1337120
Chicago Sarıkaya, Hayriye, Elif Önder, Nazlı Çil, Ergun Mete, and Gülçin Abban Mete. “Determination of MTOR Activity Depending on Donor Age of Mesenchymal Stem Cells Isolated from Adipose Tissue”. Pamukkale Medical Journal 16, no. 4 (October 2023): 704-14. https://doi.org/10.31362/patd.1337120.
EndNote Sarıkaya H, Önder E, Çil N, Mete E, Abban Mete G (October 1, 2023) Determination of mTOR activity depending on donor age of mesenchymal stem cells isolated from adipose tissue. Pamukkale Medical Journal 16 4 704–714.
IEEE H. Sarıkaya, E. Önder, N. Çil, E. Mete, and G. Abban Mete, “Determination of mTOR activity depending on donor age of mesenchymal stem cells isolated from adipose tissue”, Pam Med J, vol. 16, no. 4, pp. 704–714, 2023, doi: 10.31362/patd.1337120.
ISNAD Sarıkaya, Hayriye et al. “Determination of MTOR Activity Depending on Donor Age of Mesenchymal Stem Cells Isolated from Adipose Tissue”. Pamukkale Medical Journal 16/4 (October 2023), 704-714. https://doi.org/10.31362/patd.1337120.
JAMA Sarıkaya H, Önder E, Çil N, Mete E, Abban Mete G. Determination of mTOR activity depending on donor age of mesenchymal stem cells isolated from adipose tissue. Pam Med J. 2023;16:704–714.
MLA Sarıkaya, Hayriye et al. “Determination of MTOR Activity Depending on Donor Age of Mesenchymal Stem Cells Isolated from Adipose Tissue”. Pamukkale Medical Journal, vol. 16, no. 4, 2023, pp. 704-1, doi:10.31362/patd.1337120.
Vancouver Sarıkaya H, Önder E, Çil N, Mete E, Abban Mete G. Determination of mTOR activity depending on donor age of mesenchymal stem cells isolated from adipose tissue. Pam Med J. 2023;16(4):704-1.

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