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Today, The Visible Embryo is linked to over 600 educational institutions and is viewed by more than 1 million visitors each month. The field of early embryology has grown to include the identification of the stem cell as not only critical to organogenesis in the embryo, but equally critical to organ function and repair in the adult human. The identification and understanding of genetic malfunction, inflammatory responses, and the progression in chronic disease, begins with a grounding in primary cellular and systemic functions manifested in the study of the early embryo.

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Pregnancy Timeline by SemestersFetal liver is producing blood cellsHead may position into pelvisBrain convolutions beginFull TermWhite fat begins to be madeWhite fat begins to be madeHead may position into pelvisImmune system beginningImmune system beginningPeriod of rapid brain growthBrain convolutions beginLungs begin to produce surfactantSensory brain waves begin to activateSensory brain waves begin to activateInner Ear Bones HardenBone marrow starts making blood cellsBone marrow starts making blood cellsBrown fat surrounds lymphatic systemFetal sexual organs visibleFinger and toe prints appearFinger and toe prints appearHeartbeat can be detectedHeartbeat can be detectedBasic Brain Structure in PlaceThe Appearance of SomitesFirst Detectable Brain WavesA Four Chambered HeartBeginning Cerebral HemispheresFemale Reproductive SystemEnd of Embryonic PeriodEnd of Embryonic PeriodFirst Thin Layer of Skin AppearsThird TrimesterSecond TrimesterFirst TrimesterFertilizationDevelopmental Timeline
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Home | Pregnancy Timeline | News Alerts |News Archive May 28, 2014

 

1) Multiple sclerosis (MS) impairs nerve function by damaging myelin,
the insulating layer surrounding nerves. MS mice can't move well.
2) Human neural stem cells injected into MS mice stimulate
the mouse's own cells to repair myelin damage.
3) Nerve cell function is restored. MS mice can walk and run.
Image credit: University of Utah Health Sciences Office of Public Affairs

 

 






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Mice with MS walk after human stem cell transfer

Mice severely disabled by a condition similar to multiple sclerosis (MS) were able to walk less than two weeks following treatment with human neural stem cells.

The finding, which uncovers potential new avenues for treating MS, was published May 15, 2014, in the journal Stem Cell Reports.

In striking contrast to active, healthy mice, those with an MS-like condition must be fed by hand because they cannot stand long enough to eat and drink on their own. When scientists transplanted human neural precursor stem cells (hNPCs) into the MS mice, they expected no benefit from the treatment. They thought the mice would reject the cells as in an organ transplant.

What was to be a routine experiment instead yielded spectacular results on the first try.


“My postdoctoral fellow Dr. Lu Chen came to me and said, ‘The mice are walking.’ I didn’t believe her,”

Tom Lane, PhD, professor, pathology, University of Utah, author along with Lu Chen, PhD, University of California, Irvine.


Within a remarkably short period of time, 10 to 14 days, the mice had regained motor skills. Six months later, they showed no signs of regression.

“This result opens up a whole new area of research for us — to figure out why it worked!” remarked Jeanne Loring, Ph.D., co-senior author and director of the Center for Regenerative Medicine at The Scripps Research Institute in La Jolla, Calif. “We’ve long forgotten our original plan.”

More than 2.3 million people worldwide have MS, a disease in which the immune system attacks myelin the insulation layer surrounding nerve fibers. The resulting damage inhibits transmission of nerve impulses, producing a wide array of symptoms including difficulty walking, impaired vision, fatigue and pain.

Current FDA-approved medications slow early forms of the disease by dampening attacks from the immune system. In recent years, scientists have turned their attention to searching for ways to stop or reverse MS. Such a discovery could help patients with latter, or progressive, stages of the disease, for whom there are no treatments.

Results from the study demonstrated the mice experienced at least a partial reversal of symptoms. Immune attacks were blunted and the damaged myelin was repaired, explaining their dramatic recovery. “The way we made the neural stem cells turns out to be important,” said Loring, describing the reason behind the novel outcome.


Prior to transplantation, graduate student Ronald Coleman followed his intuition and grew the cells so they were less crowded on the Petri dish. This change in protocol yielded an extremely potent human neural stem cell type.

The experiments have since been successfully repeated with cells produced under the same conditions, but by different research laboratories.


Lane and Loring’s original prediction that the stem cells would be rejected by the immunce systems of the mice, came true. As early as one week post-treatment, there were no signs of the transplanted stem cells in the mice. Which turned out to be a significant advantage.

Human neural stem cells send out molecular signals instructing a mouse to repair damage caused by MS. Experiments by Lane’s team suggest that TGF-beta proteins make up one of those signals, but there are likely more — a realization with implications for clinical trials.

“Rather than engrafting stem cells into a patient, challenging from a medical standpoint, we might be able to develop a drug to deliver the therapy much more easily,” said Lane.

With clinical trials as the long-term goal, the next steps are to assess the durability and safety of the stem cell therapy in mice.

“We want to move as quickly, but carefully, as possible,” Lane continued. “I would love to see something that promotes repair while easing the burden on MS patients.”

Highlights
•Spinal cord transplantation of hNPCs results in recovery in a viral model of MS
•hNPC-mediated recovery occurs in the absence of engrafted cells
•hNPCs are immunomodulatory through increasing the frequency of Tregs in the CNS
•hNPCs increase Treg frequency via a TGF-β1- and TGF-β2-dependent pathway

Summary
Using a viral model of the demyelinating disease multiple sclerosis (MS), we show that intraspinal transplantation of human embryonic stem cell-derived neural precursor cells (hNPCs) results in sustained clinical recovery, although hNPCs were not detectable beyond day 8 posttransplantation. Improved motor skills were associated with a reduction in neuroinflammation, decreased demyelination, and enhanced remyelination. Evidence indicates that the reduced neuroinflammation is correlated with an increased number of CD4+CD25+FOXP3+ regulatory T cells (Tregs) within the spinal cords. Coculture of hNPCs with activated T cells resulted in reduced T cell proliferation and increased Treg numbers. The hNPCs acted, in part, through secretion of TGF-β1 and TGF-β2. These findings indicate that the transient presence of hNPCs transplanted in an animal model of MS has powerful immunomodulatory effects and mediates recovery. Further investigation of the restorative effects of hNPC transplantation may aid in the development of clinically relevant MS treatments.

In addition to Lane, Loring, Chen, and Coleman, the other authors on the publication are Ronika Leang, Alexandra Kopf, Craig Walsh, and Oswald Steward (UC Irvine), Ilse Sears-Kraxberger (TSRI), and Wendy B. Macklin (University of Colorado, Aurora).

Listen to an interview with Tom Lane about his research on The Scope Radio
http://healthcare.utah.edu/the-scope/shows.php?shows=0_lkg4ebnt

The research was funded by the National Multiple Sclerosis Society and the California Institute of Regenerative Medicine.

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