More than one-and-a-half years after implantation, researchers at University of California San Diego School of Medicine and the San Diego Veterans Administration Medical Center report that human neural stem cells (NSCs) grafted into spinal cord injuries in laboratory rats displayed continued growth and maturity, with functional recovery beginning one year after grafting.
The findings are published in the September issue of the Journal of Clinical Investigation.
The NSCs retained an intrinsic human rate of maturation despite being placed in a traumatic rodent environment, said Paul Lu, PhD, associate professor of neurosciences and lead author of the study. Thats a finding of great importance in planning for human clinical trials.
Neural stem cells differentiate into neurons and glia or support cells. Researchers like Lu and colleague, Mark Tuszynski, MD, PhD, professor of neuroscience and director of the UC San Diego Translational Neuroscience Institute, have explored their potential as a sort of patch and remedy for spinal cord injuries, implanting NSCs derived from induced pluripotent stem cells into animal models of spinal cord injuries to repair damage. In previously published animal studies, Lu and Tuszynski have shown NSCs can survive implantation and make new connections, even beginning to restore limited physical function, such as foot movement, that had been lost to paralyzing injury.
But major questions remained: At what rate do the NSCs mature? And for how long? Rat biology works at a much faster pace than human. The gestational period for a human is 280 days; for a rat, its 21. The brain of a 2- or 3-year-old human child is comparable in body/brain weight ratios to a 20-day-old rat. It was possible that human NSCs in animal models would not accurately reflect functioning in future human patients.
Most NSC grafting studies have been short-term, measuring survival times in weeks to a few months, said Tuszynski. Thats not enough time to fully measure the growth and maturation rate of human NSCs or what changes might occur farther out from the original grafting. These are important considerations, not just for the basic science of stem cell biology, but for the practical design of translational human trials using NSCs for spinal cord injuries. We need to better understand the long-term nature and time course so that we can accurately assess results and success.
Lu and colleagues used the widely available, well-characterized H9 human NSC line derived from human embryonic stem cells. The H9 NSCs were modified to express green fluorescent protein and embedded in fibrin matrices containing a growth factor cocktail. The matrices were then transplanted into spinal cord lesions of immunodeficient rats two weeks after injury, which had impaired functioning of the forelimb. Control rats underwent a similar process, but without the NSCs.
The scientists then monitored growth and development of the implanted grafts over time, noting significant early, unrefined growth followed by the appearance of markers indicating maturing nerve cells after several months. As the grafts aged, the cells continued to display gradual, normal development processes, including natural pruning and redistribution to focus development on fewer but more mature cells.
To our surprise, we found evidence of continued stem cell maturation throughout the period, said Lu. It was clear that these neural stem cells retained their intrinsic maturation programs despite a prolonged presence in a challenging environment. The recovery of forelimb function in the rats supports the basic therapeutic idea, but importantly, improvement occurred only after mature cell markers of both neuronal and glial lineages were expressed.
The lengthy study reported other findings of note: Implanted NSCs did not migrate from their lesion sites, but supportive astrocytes did, a potential safety concern. However, the scientists did not observe any adverse effects from glial outgrowth, such as tumor formation or deterioration of forelimb function over time. Tuszynski said modified grafting procedures could minimize cell leakage.
The bottom line is that clinical outcome measures for future trials need to be focused on long time points after grafting, said Tuszynski. Reliance on short time points for primary outcome measures may produce misleadingly negative interpretation of results. We need to take into account the prolonged developmental biology of neural stem cells. Success, it would seem, will take time.
Co-authors of this study are: Steven Ceto, Yaozhi Wang, Lori Graham, Di Wu, Hiromi Kumamaru, and Eileen Staufenberg, all at UC San Diego.
Funding for this research came, in part, from the Veterans Administration, the National Institutes of Health (NS09881, EB014986), the Craig H. Neilsen Foundation, the California Institute for Regenerative Medicine, the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation and the Bernard and Anne Spitzer Charitable Trust.
Read the original post:
It's Not a Rat's Race for Human Stem Cells Grafted to Repair Spinal Cord Injuries - UC San Diego Health
- Politics of Stem Cell Research - May 7th, 2011 [May 7th, 2011]
- Obama Ends Funding Ban for Stem Cell Research - May 8th, 2011 [May 8th, 2011]
- Stem Cell Research: A Father's Fight - May 10th, 2011 [May 10th, 2011]
- Human Embryonic stem cell research - May 11th, 2011 [May 11th, 2011]
- Frost Over The World - Stem Cell Research and Turkey -26 Oct - May 20th, 2011 [May 20th, 2011]
- McCain Favors Embryonic Stem Cell Research - May 20th, 2011 [May 20th, 2011]
- US divided over stem cell research reversal - 09 Mar 09 - May 21st, 2011 [May 21st, 2011]
- The Politics and Promise of Stem Cell Research - May 22nd, 2011 [May 22nd, 2011]
- Inside Story - Obama to end stem cell research ban - March 9 - Part1 - May 30th, 2011 [May 30th, 2011]
- Cardiovascular Therapies: Spotlight on Stem Cell Research - Douglas Boyd - June 3rd, 2011 [June 3rd, 2011]
- The Human Embryo and Embryonic Stem Cell Biology: Spotlight on Stem Cell Research - June 3rd, 2011 [June 3rd, 2011]
- US appeals court lifts stem cell research ban - June 7th, 2011 [June 7th, 2011]
- Trailer for Mapping Stem Cell Research: Terra Incognita - June 9th, 2011 [June 9th, 2011]
- Politics: President Obama on Stem Cell Research - June 10th, 2011 [June 10th, 2011]
- Stem Cell Research Documentary - June 11th, 2011 [June 11th, 2011]
- TEDxSingapore - Susan Lim - Hype and hope of stem cell research - June 13th, 2011 [June 13th, 2011]
- Lou Gehrig's Disease (ALS): Spotlight on Stem Cell Research - Wrapup - June 14th, 2011 [June 14th, 2011]
- The Next Frontier in Stem Cell Research - June 17th, 2011 [June 17th, 2011]
- Robert Klein: Stem Cell Research - June 22nd, 2011 [June 22nd, 2011]
- Fibrocell Stem-Cell Wrinkle Smoother Wins FDA Clearance - June 23rd, 2011 [June 23rd, 2011]
- The Politics of Stem Cell Research - June 23rd, 2011 [June 23rd, 2011]
- A Dose of Reality on Alternative Stem Cell Treatments: What you don't know can hurt you - June 28th, 2011 [June 28th, 2011]
- Governor Tim Pawlenty Discusses Stem Cell Research - June 30th, 2011 [June 30th, 2011]
- The EU and stem cell research - July 5th, 2011 [July 5th, 2011]
- Parkinson's Disease: Spotlight on Stem Cell Research - Jeff Bronstein - July 6th, 2011 [July 6th, 2011]
- Cardiovascular Therapies: Spotlight on Stem Cell Research - Yung-Wei Chi - July 7th, 2011 [July 7th, 2011]
- Spotlight on Cancer Stem Cell Research - July 11th, 2011 [July 11th, 2011]
- A Stem Cell Story - July 12th, 2011 [July 12th, 2011]
- Bishop Blair bars support for Komen breast cancer group - July 13th, 2011 [July 13th, 2011]
- Stem Cell Research In Toronto - July 14th, 2011 [July 14th, 2011]
- Arthritis: Spotlight on Stem Cell Research - Introduction - July 14th, 2011 [July 14th, 2011]
- Huntington's Disease: Spotlight on Stem Cell Research 2007 - Han Keirstead - July 15th, 2011 [July 15th, 2011]
- TMconfUK2011-08 - Stem Cell Research in the UK - Prof Charles Ffrench-Constant - July 16th, 2011 [July 16th, 2011]
- UCSF opens stem cell research building - July 16th, 2011 [July 16th, 2011]
- HIV/AIDS: Spotlight on Stem Cell Research - John Zaia - July 17th, 2011 [July 17th, 2011]
- Deafness: Spotlight on Stem Cell Research - Ebenezer Yamoah - July 22nd, 2011 [July 22nd, 2011]
- Spotlight on Basic Stem Cell Research - Irv Weissman - July 25th, 2011 [July 25th, 2011]
- Diabetes: Spotlight on Stem Cell Research - Peter Butler - July 27th, 2011 [July 27th, 2011]
- Parkinson's Disease: Spotlight on Stem Cell Research - Arnold Kriegstein - July 27th, 2011 [July 27th, 2011]
- HIV/AIDS: Spotlight on Stem Cell Research - Loren Leeds - July 27th, 2011 [July 27th, 2011]
- Alzheimer's Disease: Spotlight on Stem Cell Research - Leeza Gibbons - August 2nd, 2011 [August 2nd, 2011]
- Geron's Embryonic Stem Cell Clinical Trial for Spinal Cord Injury - August 3rd, 2011 [August 3rd, 2011]
- The Skin Gun stem cell research - August 10th, 2011 [August 10th, 2011]
- Deafness: Spotlight on Stem Cell Research - Karen Doyle - August 10th, 2011 [August 10th, 2011]
- Stem Cell Research: Huntington's Disease - August 14th, 2011 [August 14th, 2011]
- Adult and Non-Embryonic Stem Cell Research Conference at Notre Dame - August 20th, 2011 [August 20th, 2011]
- Stemcell Research and Aging - Panel 1 - August 22nd, 2011 [August 22nd, 2011]
- Texans for Stem Cell Research Learn for Life: KXAN Coverage Aired August 16th, 2011 - August 24th, 2011 [August 24th, 2011]
- Stem Cell Research: Macular Degeneration - September 18th, 2011 [September 18th, 2011]
- Brilliant Minds - Stem Cell Research | Tomorrow Today - September 25th, 2011 [September 25th, 2011]
- Ethics of Stem Cell Research (1) - September 29th, 2011 [September 29th, 2011]
- Legal and Public Policy Dimensions of Stem Cell Research - September 29th, 2011 [September 29th, 2011]
- Stem cell symposium - October 2nd, 2011 [October 2nd, 2011]
- StemCONN 2011, The Latest in Stem Cell Research - October 6th, 2011 [October 6th, 2011]
- Arthritis: Spotlight on Stem Cell Research - Mark Genovese - October 7th, 2011 [October 7th, 2011]
- Judy Roberson: Patient advocates drive stem cell scientists - October 8th, 2011 [October 8th, 2011]
- Sam Harris - Stem Cells and Morality - October 8th, 2011 [October 8th, 2011]
- Stem Cell Research, Ethics and Religion - October 9th, 2011 [October 9th, 2011]
- Stem Cells: Fulfilling the Promise - 2011 CIRM Grantee Meeting - October 10th, 2011 [October 10th, 2011]
- The Skin Gun (Stem Cell research to replace burnt off skin. Done in 3 days!) - October 13th, 2011 [October 13th, 2011]
- Alzheimer's Stem Cell Research Patient Advocate Spotlight: The Faces of Neurodegenerative Disease - Video - October 18th, 2011 [October 18th, 2011]
- Life in the Balance: Perspectives on Stem Cell Research - Video - October 18th, 2011 [October 18th, 2011]
- Stem Cell Research Funding Halt - Video - October 19th, 2011 [October 19th, 2011]
- Vatican lending hand in adult stem cell research - Video - October 20th, 2011 [October 20th, 2011]
- First Spinal-Cord Surgery With Stem Cells - Video - October 21st, 2011 [October 21st, 2011]
- Michael J. Fox Embryonic Stem Cell Research - Video - October 22nd, 2011 [October 22nd, 2011]
- stem cell research - Video - October 22nd, 2011 [October 22nd, 2011]
- Gayle Atteberry - Cloning - November 5th, 2011 [November 5th, 2011]
- It Takes Nerve: UC Irvine - Sue - November 6th, 2011 [November 6th, 2011]
- Embryonic Stem Cell Research - Video - November 9th, 2011 [November 9th, 2011]
- Adult Stem Cell Research Far Ahead of Embryonic - Video - November 10th, 2011 [November 10th, 2011]
- Is stem cell research a growing concern .flv - Video - November 10th, 2011 [November 10th, 2011]
- Forbes Discusses Stem Cell Research - Video - November 14th, 2011 [November 14th, 2011]
- Stem Cell Research Presentation - Video - November 16th, 2011 [November 16th, 2011]
- Benedict XVI: No embryonic stem cell research - Video - November 28th, 2011 [November 28th, 2011]
- Batten Disease: Spotlight on Stem Cell Research - A Father's Story - Video - November 30th, 2011 [November 30th, 2011]
- CIS 111 Digital Media Project - Stem Cell Research - Video - December 13th, 2011 [December 13th, 2011]
- Regenerative Medicine and Applications of Stem Cell Research - Video - December 20th, 2011 [December 20th, 2011]
- Stem Cell Research Today: Larry Goldstein - CIRM Science Writer's Seminar - Video - December 22nd, 2011 [December 22nd, 2011]
- CIRM Bridges Award: Building California's Stem Cell Research Workforce - Video - December 22nd, 2011 [December 22nd, 2011]