A research group from Kobe, Japan at the RIKEN Center for Molecular Imaging Science and collaborators from Osaka, Kyoto, and Tokyo have successfully differentiated bone marrow mesenchymal stem cells (MSCs) into dopamine-making neurons (the kind that die off during Parkinson’s disease), and transplanted them into macaques (a type of monkey shown below) that have Parkinson’s disease. The implanted cells relieved the motor symptoms of Parkinson’s disease. This is a remarkable proof-of-priniciple publication.
Parkinson’s disease causes a variety of motor (motor simply means associated with voluntary movement) problems. Parkinson’s disease patients have tremors, rigidity, slowness of movement, and difficulty walking. These symptoms result from the death of neurons in the midbrain that make a neurotransmitter called dopamine. Dopamine-making neurons in the midbrain are connected to regions in the cerebral cortex that help coordinate voluntary movement. Without these dopamine-making neurons, voluntary movement suffers and the characteristic symptoms of Parkinson’s disease ensue.
Several experiments have shown that replacing the dead dopamine-making neurons with manufactured neurons is feasible, but finding the right stem cell to do this has been laborious. In this new publication, a collaborative research team from Japan, led by Takuya Hayashi at the RIKEN center for Molecular Imaging Science in Kobe used a very versatile stem cell from bone marrow called the mesenchymal stem cell (also known as a stromal stem cell) for this experiment. MSCs, particularly those from bone marrow, have been used in many different regenerative medical experiments and clinical trials. However, the ability of MSCs to form neurons remains rather controversial. Even though researchers could get MSCs to form cells that looked like neurons in culture, several labs have presented observations that challenge this notion. Nevertheless, several groups have used genetic engineering techniques to place specific genes into MSCs, and these introduced genes do push MSCs to become not only neurons, but dopamine-making neurons (for papers, see Dezawa M, et al. J Clin Invest. 2004 113(12):1701–10, and Nagane K, et al., Tissue Eng Part A. 2009;15(7):1655–65).
Once it was confirmed that Hayashi and his co-workers had indeed made dopamine-making neurons from the MSCs, they were surgically transplanted into the brains of macaques that had been given a drug-induced form of Parkinson’s disease. Those animals that received the dopamine-making neurons made from bone marrow MSCs showed significant improvement in motor defects.
Did the cells integrate into the brain? Clearly they did. PET scans of the animal’s brains showed that the implanted cells were metabolically active and making dopamine. Further postmortem examination of the macaque brains confirmed that the implanted cells were still in the brains after seven months. Also, the PET scans and postmortem examination also confirmed that none of the implanted animals had any tumors or showed changes in blood chemistry. Thus the implanted cells improved symptoms, integrated into the brain. and did not produce any significant side effects or tumors.
This paper nicely illustrates that it is entirely possible to treat a patient’s Parkinson’s disease with cells from their own bone marrow in a manner that is safe and relatively effective.