Skip to main content
SpringerLink
Log in

In vitro preconditioning of insulin-producing cells with growth factors improves their survival and ability to release insulin

  • Published:
Journal of Biosciences Aims and scope Submit manuscript

Abstract

Glucose-induced oxidative stress in the diabetic pancreas directly affects viability and the consequent therapeutic outcome of transplanted stem cells. Pretreatment of stem cells with growth factors induces tolerance in them against various stresses (hypoxia, thermal or hyperglycaemic). This study investigated the effect of pretreatment on insulin-producing cells (IPCs) differentiated from adipose-derived mesenchymal stem cells (ADMSCs), with a combination of stromal cell-derived factor 1 alpha (SDF1α) and basic fibroblast growth factor (bFGF) against hyperglycaemic stress (17 or 33 mM glucose). The results showed that IPCs pretreated with a combination of SDF1α and bFGF exhibited maximally alleviated apoptosis, senescence and cell damage with a concomitantly increased release of insulin, enhanced cell proliferation and greater up-regulation of Insulin 1, Insulin 2, Ngn3, Pdx1 and Nkx6.2 when stressed with 33 mM glucose. These findings may offer an improved therapeutic outcome for the treatment of diabetes.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6

Similar content being viewed by others

Abbreviations

ADMSCs:

adipose-derived mesenchymal stem cells

bFGF:

basic fibroblast growth factor

IPCs:

insulin-producing cells

SDF1α:

stromal cell-derived factor 1 alpha

References

  • Ahmad MR, Mehmood A, Bhatti FU, Khan SN and Riazuddin S 2014 Combination of ADMSCs and chondrocytes reduces hypertrophy and improves the functional properties of osteoarthritic cartilage. Osteoarthr. Cartil. 22 1894–901

    Article  Google Scholar 

  • Ali M, Mehmood A, Anjum MS, Tarrar MN, Khan SN and Riazuddin S 2015 Diazoxide preconditioning of endothelial progenitor cells from streptozotocin-induced type 1 diabetic rats improves their ability to repair diabetic cardiomyopathy. Mol. Cell. Biochem. 410 267–79

    Article  PubMed  CAS  Google Scholar 

  • Allahverdi A, Abroun S, Jafarian A, Soleimani M, Taghikhani M and Eskandari F 2015 Differentiation of human mesenchymal stem cells into insulin producing cells by using a lentiviral vector carrying PDX1. Cell J. (Yakhteh) 17 231–242

    Google Scholar 

  • Baer PC 2014 Adipose-derived mesenchymal stromal/stem cells: an update on their phenotype in vivo and in vitro. World J. Stem Cells 6 256–65

    Article  PubMed  PubMed Central  Google Scholar 

  • Bai Y, Li P, Yin G, Huang Z, Liao X, Chen X and Yao Y 2013 BMP-2, VEGF and bFGF synergistically promote the osteogenic differentiation of rat bone marrow-derived mesenchymal stem cells. Biotechnol. Lett. 35 301–308

    Article  PubMed  CAS  Google Scholar 

  • Bastidas-Ponce A, Scheibner K, Lickert H and Bakhti M 2017 Cellular and molecular mechanisms coordinating pancreas development. Development 144 2873–2888

    Article  PubMed  CAS  Google Scholar 

  • Berezin AE 2014 Diabetes mellitus and cellular replacement therapy: expected clinical potential and perspectives. World J. Diabetes 5 777–786

    Article  PubMed  PubMed Central  Google Scholar 

  • Calafiore R, Montanucci P and Basta G 2014 Stem cells for pancreatic beta-cell replacement in diabetes mellitus: actual perspectives. Curr. Opin. Organ. Transplant 19 162–168

    Article  PubMed  CAS  Google Scholar 

  • Chandra V, Swetha G, Muthyala S, Jaiswal AK, Bellare JR, Nair PD and Bhonde RR 2011 Islet-like cell aggregates generated from human adipose tissue derived stem cells ameliorate experimental diabetes in mice. PLoS One 6 e20615

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Crowley LC, Marfell BJ, Scott AP and Waterhouse NJ 2016 Quantitation of apoptosis and necrosis by annexin v binding, propidium iodide uptake, and flow cytometry. Cold Spring Harb. Protoc. 2016: pdb.prot087288

  • Czubak P, Bojarska-Junak A, Tabarkiewicz J and Putowski L 2014 A modified method of insulin producing cells’ generation from bone marrow-derived mesenchymal stem cells. J. Diabetes Res. 2014 628591

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Dang LT-T, Bui AN-T, Pham VM, Phan NK and Pham PV 2015 Production of islet-like insulin-producing cell clusters in vitro from adipose-derived stem cells. Biomed. Res. Ther. 2 184–192

    Article  Google Scholar 

  • Dave SD, Vanikar AV and Trivedi HL 2013 Extrinsic factors promoting in vitro differentiation of insulin-secreting cells from human adipose tissue-derived mesenchymal stem cells. Appl. Biochem. Biotechnol. 170 962–971

    Article  PubMed  CAS  Google Scholar 

  • Gabr MM, Zakaria MM, Refaie AF, Khater SM, Ashamallah SA, Ismail AM, El-Halawani SM and Ghoneim MA 2015 Differentiation of human bone marrow-derived mesenchymal stem cells into insulin-producing cells: evidence for further maturation in vivo. Biomed. Res. Int. 2015 10

    Article  CAS  Google Scholar 

  • Guo W, Miao C, Liu S, Qiu Z, Li J and Duan E 2009 Efficient differentiation of insulin-producing cells from skin-derived stem cells. Cell Prolif. 42 49–62

    Article  PubMed  CAS  Google Scholar 

  • Hebert TL, Wu X, Yu G, Goh BC, Halvorsen YDC, Wang Z, Moro C and Gimble JM 2009 Culture effects of epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF) on cryopreserved human adipose-derived stromal/stem cell proliferation and adipogenesis. J. Tissue Eng. Regen. Med. 3 553–561

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Huang Q, Bu S, Yu Y, Guo Z, Ghatnekar G, Bu M, Yang L, Lu B, Feng Z, Liu S and Wang F 2007 Diazoxide prevents diabetes through inhibiting pancreatic b-cells from apoptosis via Bcl-2/Bax rate and p38-Mitogen-activated protein kinase. Endocrinology 148 81–91

    Article  PubMed  CAS  Google Scholar 

  • Jian R-L, Mao L-B, Xu Y, Li X-F, Wang F-P, Luo X-G, Zhou H, He H-P, Wang N and Zhang T-C 2015 Generation of insulin-producing cells from C3H10T1/2 mesenchymal progenitor cells. Gene 562 107–116

    Article  PubMed  CAS  Google Scholar 

  • Khan M, Akhtar S, Mohsin S, Khan SN and Riazuddin S 2011 Growth factor preconditioning increases the function of diabetes-impaired mesenchymal stem cells. Stem Cells Dev. 20 67–75

    Article  PubMed  CAS  Google Scholar 

  • Khan M, Ali F, Mohsin S, Akhtar S, Mehmood A, Choudhery MS, Khan SN and Riazuddin S 2013 Preconditioning diabetic mesenchymal stem cells with myogenic medium increases their ability to repair diabetic heart. Stem Cell Res. Ther. 4 58

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Kim SC, Han DJ and Lee JY 2010 Adipose tissue derived stem cells for regeneration and differentiation into insulin-producing cells. Curr. Stem. Cell Res. Ther. 5 190–194

    Article  PubMed  CAS  Google Scholar 

  • Liu X, Wang Y, Li Y, Pei X 2013 Research status and prospect of stem cells in the treatment of diabetes mellitus. Sci. China Life Sci. 3 306–312

    Article  CAS  Google Scholar 

  • Lu Q, Wang C, Pan R, Gao X, Wei Z, Xia Y and Dai Y 2013 Histamine synergistically promotes bFGF-induced angiogenesis by enhancing VEGF production via H1 receptor. J. Cell. Biochem. 114 1009–1019

    Article  PubMed  CAS  Google Scholar 

  • Marshall NJ, Goodwin CJ and Holt SJ 1995 A critical assessment of the use of microculture tetrazolium assays to measure cell growth and function. Growth Regul. 5 69–84

    PubMed  CAS  Google Scholar 

  • Mehmood A, Ali M, Khan SN and Riazuddin S 2015 Diazoxide preconditioning of endothelial progenitor cells improves their ability to repair the infarcted myocardium. Cell Biol. Int. 39 1251–1263

    Article  PubMed  CAS  Google Scholar 

  • Qi M 2014 Transplantation of encapsulated pancreatic islets as a treatment for patients with type 1 diabetes mellitus. Adv. Med. 2014 15

    Article  Google Scholar 

  • Raikwar SP, Kim E-M, Sivitz WI, Allamargot C, Thedens DR and Zavazava N 2015 Human iPS cell-derived insulin producing cells form vascularized organoids under the kidney capsules of diabetic mice. PLoS ONE 10 e0116582

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Rezania A, Bruin JE, Arora P, Rubin A, Batushansky I, Asadi A, O’Dwyer S, Quiskamp N, Mojibian M, Albrecht T, Yang YHC, Johnson JD and Kieffer TJ 2014 Reversal of diabetes with insulin-producing cells derived in vitro from human pluripotent stem cells. Nat. Biotechnol. 32 1121–1133

    Article  PubMed  CAS  Google Scholar 

  • Santamaria X, Massasa EE, Feng Y, Wolff E and Taylor HS 2011 Derivation of insulin producing cells from human endometrial stromal stem cells and use in the treatment of murine diabetes. Mol. Ther. 19 2065–2071

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Sun B, Liu R and Xiao Z-D 2015 Induction of insulin-producing cells from umbilical cord blood-derived stromal cells by activation of the c-Met/HGF axis. Dev. Growth Differ. 57 353–361

    Article  PubMed  CAS  Google Scholar 

  • Sun J, Mao LQ, Polonsky KS and Ren DC 2016 Pancreatic β-cell death due to Pdx-1 deficiency requires multi-BH domain protein Bax but not Bak. J. Biol. Chem. 291 13529–13534

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Tariq M, Masoud MS, Mehmood A, Khan SN and Riazuddin S 2013 Stromal cell derived factor-1alpha protects stem cell derived insulin-producing cells from glucotoxicity under high glucose conditions in vitro and ameliorates drug induced diabetes in rats. J. Transl. Med. 11 115

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Thorens B 2015 GLUT2, glucose sensing and glucose homeostasis. Diabetologia 58 221–232

    Article  PubMed  CAS  Google Scholar 

  • Tsai PJ, Wang HS, Shyr YM, Weng ZC, Tai LC, Shyu JF and Chen TH 2012 Transplantation of insulin-producing cells from umbilical cord mesenchymal stem cells for the treatment of streptozotocin-induced diabetic rats. J. Biomed. Sci. 19 47

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Uchi H, Igarashi A, Urabe K, Koga T, Nakayama J, Kawamori R, Tamaki K, Hirakata H, Ohura T and Furue M 2009 Clinical efficacy of basic fibroblast growth factor (bFGF) for diabetic ulcer. Eur. J. Dermatol. 19 461–468

    PubMed  Google Scholar 

  • Van Belle TL, Coppieters KT and von Herrath MG 2011 Type 1 diabetes: etiology, immunology, and therapeutic strategies. Physiol. Rev. 91 79–118

    Article  PubMed  CAS  Google Scholar 

  • Xiao J, Lv Y, Lin S, Jin L, Zhang Y, Wang X, Ma J, Hu K, Feng W, Cai L, Li X and Tan Y 2010 Cardiac protection by basic fibroblast growth factor from ischemia/reperfusion-induced injury in diabetic rats. Biol. Pharm. Bull. 33 444–449

    Article  PubMed  CAS  Google Scholar 

  • Xie H, Wang Y, Zhang H, Qi H, Zhou H and Li FR 2013 Role of injured pancreatic extract promotes bone marrow-derived mesenchymal stem cells efficiently differentiate into insulin-producing cells. PLoS One 8 e76056

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Zaccardi F, Webb DR, Yates T and Davies MJ 2016 Pathophysiology of type 1 and type 2 diabetes mellitus: a 90-year perspective. Postgrad. Med. J. 92 63–69

    Article  PubMed  CAS  Google Scholar 

  • Zhu FF, Zhang PB, Zhang DH, Sui X, Yin M, Xiang TT, Shi Y, Ding MX and Deng H 2011 Generation of pancreatic insulin-producing cells from rhesus monkey induced pluripotent stem cells. Diabetologia 54 2325–2336

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

This work was supported in part by a grant from the Higher Education Commission of Pakistan.

Author information

Authors and Affiliations

  1. National Centre of Excellence in Molecular Biology, University of Punjab, 87-West Canal Bank Road, Lahore, Pakistan

    Muhammad Sohail Anjum, Azra Mehmood, Faiza Mahmood, Muhammad Ali, Shaheen N. Khan & Sheikh Riazuddin

  2. Allama Iqbal Medical College, University of Health Sciences, Lahore, Pakistan

    Moazzam Nazir Tarrar & Sheikh Riazuddin

  3. Shaheed Zulfiqar Ali Bhutto Medical University (SZABMU), Islamabad, Pakistan

    Sheikh Riazuddin

Authors
  1. Muhammad Sohail Anjum
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Azra Mehmood
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Faiza Mahmood
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Muhammad Ali
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Moazzam Nazir Tarrar
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Shaheen N. Khan
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Sheikh Riazuddin
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Sheikh Riazuddin.

Additional information

Communicated by María Luz Cárdenas.

Corresponding editor: María Luz Cárdenas

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Anjum, M.S., Mehmood, A., Mahmood, F. et al. In vitro preconditioning of insulin-producing cells with growth factors improves their survival and ability to release insulin. J Biosci 43, 649–659 (2018). https://doi.org/10.1007/s12038-018-9796-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12038-018-9796-8

Keywords

Search

Navigation