title: 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.
abstract: BACKGROUND
  Diabetes mellitus is affecting more than 300 million people worldwide. Current treatment strategies cannot prevent secondary complications. Stem cells due to their regenerative power have long been the attractive target for the cell-based therapies. Mesenchymal stem cells (MSCs) possess the ability to differentiate into several cell types and to escape immune recognition in vitro. MSCs can be differentiated into insulin-producing cells (IPCs) and could be an exciting therapy for diabetes but problems like poor engraftment and survivability need to be confronted. It was hypothesized that stromal cell derived factor- 1alpha (SDF-1alpha) will enhance therapeutic potential of stem cell derived IPCs by increasing their survival and proliferation rate.
  
  
  METHODS
  Novel culture conditions were developed to differentiate bone marrow derived mesenchymal stem cells (BMSCs) into IPCs by using endocrine differentiation inducers and growth factors via a three stage protocol. In order to enhance their therapeutic potential, we preconditioned IPCs with SDF-1alpha.
  
  
  RESULTS
  Our results showed that SDF-1alpha increases survival and proliferation of IPCs and protects them from glucotoxicity under high glucose conditions in vitro. SDF-1alpha also enhances the glucose responsive insulin secretion in IPCs in vitro. SDF-1alpha preconditioning reverses hyperglycemia and increase serum insulin in drug induced diabetic rats.
  
  
  CONCLUSIONS
  The differentiation of BMSCs into IPCs and enhancement of their therapeutic potential by SDF-1alpha preconditioning may contribute to cell based therapies for diabetes.
authors: National Centre of Excellence in Molecular Biology, University of the Punjab, Lahore, Pakistan. m_awan_tariq@hotmail.com
authors: Muhammad
authors: M
authors: Tariq
authors: Muhammad Sharif
authors: MS
authors: Masoud
authors: Azra
authors: A
authors: Mehmood
authors: Shaheen N
authors: SN
authors: Khan
authors: Sheikh
authors: S
authors: Riazuddin
mesh_terms: D000818:Animals; D017209:Apoptosis; D001854:Bone Marrow Cells / Q000166:cytology; D002454:Cell Differentiation; D049109:Cell Proliferation; D002470:Cell Survival; D054377:Chemokine CXCL12 / Q000378:metabolism*; D017931:DNA Primers; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D005260:Female; D005947:Glucose / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D019394:Ki-67 Antigen / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013234:Stem Cells / Q000166:cytology*
chemical_list: C575935:CXCL12 protein, rat; D054377:Chemokine CXCL12; D017931:DNA Primers; D007328:Insulin; D019394:Ki-67 Antigen; D005947:Glucose
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