Page 552 - fbkCardioDiabetes_2017

528 Cardio Diabetes Medicine 2017

in the developing and mature retina. Neurotrophins tration of stem cells, whether targeted or peripheral,
are initially synthesized in a pro-form and undergo should be identified. In the targeted approach, de-
proteolytic cleavage to produce the mature form that termining the optimal administration method is also
activates two distinctive receptors, the tyrosine ki- important.
nase tropomycin receptor (Trk) and, to lesser extent,
the common low affinity p75 neurotrophin receptor References:
(p75NTR). Diabetes induces imbalance in neurotro- 1. International Diabetic Federation, 2016
phins by increasing its proform, which is associated
with upregulation of the p75NTR receptor in the reti- 2. Zang Li et al, Mesenchymal stem cell therapy in type 2 diabetes mellitus,
Diabetology & Metabolic Syndrome 2017 9:36
na. ProNGF/NGF imbalance is an important biomark-
er for Diabetic Retinopathy (DR) due to the reduction 3. Dor et al, Recovery from diabetes in mice by beta cell regeneration, J Clin
Invest. 2007 Sep;117(9):2553-61.
in expression and activity of MMP-7, the enzyme that
cleaves proNGF to form mature NGF resulting in ac- 4. Seaberg et al, Clonal identification of multipotent precursors from adult
mouse pancreas that generate neural and pancreatic lineages, Nat Bio-
cumulation of proNGF and decreases in NGF levels in technol. 2004 Sep;22(9):1115-24
the retina. NGF has been shown to stimulate vascular
endothelial growh factor (VEGF) production which is 5. Charles A. Goldthwaite, Jr., Ph.D. Are Stem Cells the Next Frontier for
diabetes treatment?
known regulator of vascular permeability and angio-
genesis in ocular diseases including DR. Diabetes-in- 6. Estrada et al, Combined treatment of intrapancreatic autologous bone
marrow stem cells and hyperbaric oxygen in type 2 diabetes mellitus, Cell
duced breakdown of the blood retina barrier was as- Transplant. 2008;17(12):1295-304.
sociated with increases in proNGF and decreases in
NGF. 7. Juventas Clinic Germany, between February 2010- June 2010
8. Pittenger G. et al, Nerve Growth Factor and Diabetic Neuropathy, Exper-
Diabetes-induced imbalance of proNGF/NGF result- imental Diab. Res., 4:271–285, 2003
ed in upregulation of proNGF/ p75NTR axis and
downregulation of NGF/TrkA axis. This imbalance
appears to play critical role in early pathogenesis
of DR such as retinal neurodegeneration, inflamma-
tion and vascular dysfunction that eventually leads
to blindness. Restoring balance between proneuro-
trophin/mature neurotrophin represents a potential
promising therapeutic strategy to overcome retinal
degenerative diseases including DR. (8)

3.Side Effects:
A low incidence of punctural hemorrhage, posttrau-
matic pain, and subcutaneous hematoma at the
injection site following intrapancreatic MSC trans-
plantation was reported. Mild and moderate fever
with spontaneous remission after transvenous MSC
transplantation was reported in 13.6–22.2% of patients.
Transient self-limiting nausea, vomiting, headache,
abdominal pain, and upper respiratory tract infection
occasionally occurred after the MSC transplantation.
(2)

4.Conclusion:
Longer disease duration, older age, poor islet func-
tion and other complications of T2DM were asso-
ciated with a less conducive microenvironment for
transplanted cells. Duration of DM, residual beta-cell
function, and the severity of complications will affect
treatment efficacy. Thus, the method of selection of
appropriate patients for this treatment needs to be
determined. In addition, the ideal route of adminis-

GCDC 2017