Improving transplanted dopamine neuron survival using biomaterials

Original article: Encapsulation of young donor age dopaminergic grafts in a GDNF-loaded collagen hydrogel further increases their survival, reinnervation, and functional efficacy after intrastriatal transplantation in hemi-Parkinsonian rats, The European Journal of Neuroscience: July 27, 2018. 

The takeaway

Coating cells to be transplanted directly into the brain with a GDNF (or Glial cell-derived neurotrophic factor)-loaded collagen scaffold increased their survival, and improved their ability to grow within the transplant region, which correlated with improved movement in experimental animals.

Why is it important?

This study extends previous findings on how the survival and efficacy of transplanted cells can be improved in order to achieve greater clinical benefits from cell replacement therapies.

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IMPACT

  • Novelty 75% 75%
  • Proximity 70% 70%
  • Deliverability 60% 60%

Impact Opinion

“This is a very intriguing approach to regenerative therapy for Parkinson’s – combining both cell replacement therapy and neurotrophic factors. The researchers have demonstrated that this method can markedly increase cell survival within the transplanted graft. It would be interesting to assess whether this approach could also have beneficial effects on the remaining dopamine neurons in the midbrain in the Parkinsonian brain.”

Background

We have known for several years from preclinical studies that transplanted embryonic dopaminergic neurons in the brain can, in principle, survive, grow and function. However, the actual clinical benefits seen in clinical trials in people with Parkinson’s have been disappointing, mostly due to poor survival and inadequate growth of these transplanted cells. Researchers have been investigating whether providing “scaffolds” using different biomaterials such as collagen can improve cell survival, and finding that indeed, they can. But how can we achieve further progress and further improve neuron survival to ensure that clinical benefit may be seen in a future trial?

The details

In this study, the researchers used rat embryonic neurons in an animal model of Parkinson’s. They transplanted these neurons into the brains of 4 groups of experimental animals, which received the neurons either: 1) alone, 2) encased in a collagen scaffold, 3) along with an infusion of GDNF, or 4) encased in a collagen hydrogel scaffold that had additionally been loaded with GDNF. GDNF is a naturally occurring trophic factor (a protective/supportive protein) produced by glial cells in the brain, which effectively helps neurons grow and survive.

Twelve weeks later, the researchers studied both the animals’ behaviour as well as the extent to which the transplanted cells had grown. They found that the GDNF-loaded collagen scaffold led to a four-fold increase in dopamine neuron survival, and a greater than five-fold increase in growth in the critical movement-related brain region, the striatum, into which the neurons had been implanted. The improved neuronal growth also correlated with the improvement seen in movement recovery on behavioural tests.  

Next steps

Given the recent developments and current trial using induced pleuripotent stem cells (iPSCs) derived from skin cells, the next steps would be to address how these biomaterials can improve their survival and growth also.  

Original article: Encapsulation of young donor age dopaminergic grafts in a GDNF-loaded collagen hydrogel further increases their survival, reinnervation, and functional efficacy after intrastriatal transplantation in hemi-Parkinsonian rats, The European Journal of Neuroscience: July 27, 2018. 

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