From stem cells to beta cells possible cure for diabetes mellitus
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From Stem Cells to Beta Cells: Possible Cure for Diabetes Mellitus. By Ryan Scavinski. Diabetes Mellitus. Type 1 Diabetes is caused by the autoimmune destruction of β -cells within the pancreas. No β -cells, no insulin Diabetics need to monitor blood glucose and control it with insulin.

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Presentation Transcript

Diabetes mellitus
Diabetes Mellitus Mellitus

  • Type 1 Diabetes is caused by the autoimmune destruction of β-cells within the pancreas.

  • No β-cells, no insulin

  • Diabetics need to monitor blood glucose and control it with insulin.


Past treatments
Past Treatments Mellitus

  • Transplantation of pancreatic islet cells

  • Problems

    • Patient requires more than 600 islets/kg body weight = two deceased organ donors

    • Immunological rejection


Using stem cells
Using Stem Cells Mellitus

  • Two approaches used to differentiate Embryonic Stem Cells into β-cells or Insulin Producing Cells (IPCs)

    • Embryoid Body Formation

    • Definitive Endoderm Formation


Embryoid body formation
Embryoid Body Formation Mellitus

  • An embryoid is the arrangement of stem cells destined to differentiate into the ectoderm, mesoderm and endoderm.

  • With multiple treatment of growth factors, Embryonic stem cells give rise to Nestin cells, which in turn differentiate into IPCs.


Problems
Problems Mellitus

  • Low efficiency for producing IPCs

  • Also showed development of tumors in the kidney and spleen in some transplanted mice.


Definitive endoderm approach
Definitive Endoderm Approach Mellitus

  • This approach bypasses the Embryoid formation and generates the endoderm, in which produce the cells needed for insulin production.


Differentiation steps
Differentiation Steps Mellitus

  • 1. ESCs were placed onto a culture dish with a chemically defined medium (CDM) containing 50 ng/mL Activin A for 4 days


gapd sox17 pdx1 hlxb9 hnf4α insulin


Continued
continued Mellitus

  • 2. Then the cells were transferred onto a CDM with 10-6 M Retinoic acid (RA) for another 4 days


Without Activin A and RA Mellitus

With Activin A and RA

small clusters of differentiated ES


PCR Mellitus

  • A+/RA+

  • A-/RA-

  • A+/RA-

  • A-/RA+

gapd sox17 pdx1 hlxb9 hnf4α insulin


Continued1
continued Mellitus

  • 3. Then the CDM was changed to modified islet maturation medium containing bFGF- a pancreatic cell maturation factor for 3 days

  • 4. Finally the differentiated cells were switched to a islet maturation medium containing nicotinamide and the bFGF for another 3 days.



Differentiated embryonic stem cells
Differentiated Embryonic Stem Cells spherical clusters

gapd sox17 pdx1 hlxb9 hnf4α insulin glut2 Amy SST Sur1 GCG GCK

Maturation

Control



2.5 mM buffer containing 2.5 mM glucose for 15 min

27.5 mM

Insulin secretion (ng/mg)

Suspension Adhesion


Transplantation
Transplantation buffer containing 2.5 mM glucose for 15 min

  • Differentiated cells were transplanted under the renal capsule (kidney) of diabetic mice.

  • 30% showed normal blood glucose levels for 6 weeks

  • They removed the cell transplanted kidney-mice regained hyperglycemia


30 buffer containing 2.5 mM glucose for 15 min

25

20

15

10

5

0

Blood glucose (mM)

0 7 14 21 28 35 42 49 56

Days after transplantation


Results and discussion
Results and Discussion buffer containing 2.5 mM glucose for 15 min

  • The combination of Activin A and Retinoic Acid is an effective method to induce Embryonic Stem Cells to differentiate into insulin producing cells

  • Further research in needed to see if the difference between human and mouse will impair the function of transplanted ESC derived cells


My opinion
My Opinion buffer containing 2.5 mM glucose for 15 min


  • Reference: buffer containing 2.5 mM glucose for 15 min

  • Soria, B., Skoudy, A., and Martin, F. 2001. From stem cells to beta cells: new strategies in cell therapy of diabetes mellitus. Diabetologia 44 407-415

  • Raikwar, S. and Zavazava, N. 2009. Insulin producing cells derived from embryonic stem cells: are we there yet?. Journal of Cellular Physiology, 218 256-263

  • Jiang, W., Shi, Y., Zhao, D., Chen, S., Youg, J., Zhang, J., Qing, T., Sun, X., Zhang, P., Ding, M., Li, D., and Deng, H. 2007. In vitro derivation of functional insulin producing cells from human embryonic stem cells. Cell Research. 17 333-344


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