Neural Stem Cell Transplant Treats Parkinson's in Rats

The proximate cause of the most visible symptoms of Parkinson's disease is the progressive loss of a small but vital population of dopamine-generating neurons. This loss happens to everyone, but for a variety of underlying reasons, not all of which are clear at this time, people with Parkinson's experience a more rapid loss of these cells. This is the case for many age-related medical conditions: they are a more rapid progression of a process that is in fact happening to all of us, and so the development of therapies is worth keeping an eye on. One approach to the treatment of Parkinson's disease is to attempt to restore the failing population of dopamine-generating neurons via some form of cell therapy, as demonstrated here in rats:

Parkinson's disease (PD) is considered the second most frequent and one of the most severe neurodegenerative diseases, with dysfunctions of the motor system and with nonmotor symptoms such as depression and dementia. Compensation for the progressive loss of dopaminergic (DA) neurons during PD using current pharmacological treatment strategies is limited and remains challenging. Pluripotent stem cell-based regenerative medicine may offer a promising therapeutic alternative, although the medical application of human embryonic tissue and pluripotent stem cells is still a matter of ethical and practical debate.

Addressing these challenges, the present study investigated the potential of adult human neural crest-derived stem cells derived from the inferior turbinate (ITSCs) transplanted into a parkinsonian rat model. Emphasizing their capability to give rise to nervous tissue, ITSCs isolated from the adult human nose efficiently differentiated into functional mature neurons in vitro. Transplantation of predifferentiated or undifferentiated ITSCs led to robust restoration of behavior, accompanied by significant recovery of DA neurons within the substantia nigra. ITSCs were further shown to migrate extensively in loose streams primarily toward the posterior direction as far as to the midbrain region, at which point they were able to differentiate into DA neurons within the locus ceruleus. We demonstrate, for the first time, that adult human ITSCs are capable of functionally recovering a PD rat model.

Link: http://dx.doi.org/10.5966/sctm.2014-0078

Comments

Aren't they already testing IPS derived dopamine producing neural cells in humans? What is the point of using stem cells instead? Surely they would be less effective?

Posted by: Jim at May 26th, 2015 6:49 PM

Hi Jim,

First, "they" aren't YET using such cells in clinical trials: Jeanne Loring's group is still trying to get enough funding together for their clinical trial of iPS stem cells for Parkinson's disease, and the Japanese trial led by Jun Takahashi of Kyoto University just hasn't started yet. The TRANSEURO trial is once again using fetal tissue, although in this case they are being careful to select dopaminergically-biased cells instead of just taking all the cells in a given area. As far as I know,the trial being organized jointly by Ivar Mendez (Chair of the Department of Surgery at the University of Saskatchewan) and Ole Isacson of Harvard, both of whom were principal investigators of early trials 20 years ago using crude fetal brain cell populations, is in an even earlier stage, and that proposed by Memorial Sloan Kettering neurologist Lorenz Studer is more nascent yet.

In terms of THIS study: first, note that they got the cells from adult human nose: I'm optimistic enough about iPS that I think we should expect to be able to make good use of them and to see positive results in Drs. Loring's and Takahashi's trials, but clearly we want to explore additional cell sources, and these are convenient and readily-available patient-identical cells.

And second, WHATEVER the cell source they use, there is still lots of work that can and should be done in animal models in this area, ideally in the kind of bench-to-bedside-and-back feedback loop that is the best of translational medicine, in terms of tissue preparation (number of cells grafted, better protocols to derive or isolate dopamine-biased stells from grafted or pluripotent (ESC, iPS, SCNT) cells, the right stage of maturation to engraft, tissue placement (location, tract numbers), graft support (storage media, immunotherapy after grafting), and the very critical long-term work of figuring out how to rebuild physiologic dopaminergic neuronal circuitry (these early trials are really still placing the engrafted cells ectopically, as local biological dopamine minipumps, as we haven't yet got good protocols to draw out engrafted cells over the distances required to fully recapitulate the physiological circuitry).

Posted by: Michael at May 26th, 2015 9:16 PM

Michael I am sure you are aware of this but they have turned blood cells into Neurons recently so again this is a potential REPLENIsens approach perhaps?

http://www.iflscience.com/health-and-medicine/scientists-turn-blood-cells-neurons

Stem cell technology is improving in leaps and bounds and it seems very likely they will be able to produce most differentiated and non differentiated cells ex-vivo to reintroduce them back to the body to replace lost cells soon.

I would be interested to hear your comments on the above link if you have the time to share your thoughts?

Posted by: Steve H at May 27th, 2015 6:05 AM

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