Young Girl Receives Lifesaving Windpipe Transplant Made From Her Stem Cells

Hannah Warren was born without a trachea but now has one made from plastic fibers and a stew of her own stem cells.

The 2-year-old Korean Canadian has spent every day of her life in intensive care, kept alive by a tube that substituted for the windpipe that was supposed to connect her mouth to her lungs. But nearly a month after her transplant, the toddler is mostly breathing on her own and is responding to doctors and nurses.

The surgery, pioneered by Dr. Paolo Macchiarini, director of the Advanced Center for Translational Regenerative Medicine at the Karolinska Institute in Stockholm, was only the sixth performed in the world, and Hannah was the youngest patient and first to receive the transplant in the U.S. The procedure was approved by the FDA as an experimental operation for patients with very little hope of survival; being born without a trachea is fatal in 99% of cases.

For complete article see Time.com

FDA approves Phase II of stem cell trial for ALS led by U-M’s Dr. Eva Feldman

ANN ARBOR, Mich. — For nearly two years, University of Michigan neurologist Eva Feldman, M.D., Ph.D. has led the nation’s first clinical trial of stem cell injections in patients with the deadly degenerative disease known as amyotrophic lateral sclerosis, often called ALS or Lou Gehrig’s disease.

Now, a new approval from the U.S. Food and Drug Administration paves the way for U-M to become the second site in the trial, pending approval of the U-M Institutional Review Board. To date, the first phase of the trial has taken place at Emory University, with Feldman serving as principal investigator.

The FDA approval of a Phase II trial was announced today by Neuralstem, the company whose product the trial is testing. The Phase II trial will continue to evaluate the safety of the stem cell injections, delivered directly into patients’ spinal cords in escalating doses of up to 400,000 cells per injection, with a maximum of 40 injections. It will also assess any signs that the injections might be impacting patients’ ALS symptoms or progression.

Feldman serves as an unpaid consultant to the company, and has led the analysis of results from the Phase I trial. In data presented last year, spinal cord injections of up to 100,000 cells were delivered safely and tolerated well — with possible signs that in one subgroup of participants, ALS progression may have been interrupted.

“In Phase II, we’ll be injecting stem cells into the upper part of the spinal cord, and our goal is to continue to assess whether this approach is safe, and to look at whether this approach offers some benefit to our patients. We are very pleased at the potential to bring this trial to the University of Michigan, where the initial research behind this technology was done — as well as having it continue at Emory,” says Feldman, the Russell N. DeJong Professor of Neurology at the U-M Medical School, research director of U-M’s ALS Clinic, and director of U-M’s A. Alfred Taubman Medical Research Institute. The neurosurgeon for the trial is Parag Patil, M.D, Ph.D.

The approach uses injections of stem cells delivered during an operation performed by a neurosurgeon. The first phase of the trial involved 15 patients; specific plans for Phase II are still being made but information will be available at neuralstem.com.

If the U-M site team receives IRB approval to recruit local participants, more information will be available at uofmhealth.org. The study at U-M will be funded by the ALS Association, the National Institutes of Health and Neuralstem.

New method for mass-producing RPE cells paves way to treating age-related blindness

Durham, NC – Scientists have developed a new, simpler way to produce human pluripotent stem cells in quantities large enough that they can be used to develop treatments for age-related macular degeneration — the leading cause of irreversible blindness among the elderly. The results of this new study are published in the current issue of STEM CELLS Translational Medicine.

Age-related macular degeneration (AMD), which affects up to 50 million people worldwide, is associated with the dysfunction and death of retinal pigment epithelial (RPE) cells.

“As a result, there has been significant interest in developing RPE culture systems both to study AMD disease mechanisms and to provide substrate for possible cell-based therapies. Because of their indefinite self-renewal, human pluripotent stem cells (hPSCs) have the potential to provide an unlimited supply of RPE-like cells,” noted Donald Zack, M.D., Ph.D., who with Julien Maruotti, Ph.D., led the team of researchers from the Wilmer Institute, Johns Hopkins University School of Medicine in Baltimore, Md., and the Institute of Vision in Paris in conducting the study.

“However, most of the currently accepted methods in use for deriving RPE cells from hPSC involve time-and-labor-consuming  steps done by hand, and they don’t yield large enough amount of the differentiated cells – which has posed a problem when trying to use them to develop potential new therapies,” Dr. Maruotti added.

The Zack/Maruotti team simplified RPE cell production by modifying a standard protocol for isolating the cells from spontaneously differentiating hPSC monolayers. In the new method, hPSCs were amplified by clonal propagation and the RPE cells enriched by serial passage rather than mechanical picking.

“These modifications eliminate the need for the time- and labor consuming manual steps usually required to culture hPSCs and to purify the RPE population, and thereby provide a readily scalable approach to generate large numbers of high quality RPE cells — up to 36 times more than the best protocols previously reported during the same time interval,” Dr. Zack said.

“This improved process represents a step toward mass production of RPE and could prove useful for applications requiring large number of cells such as cell therapy, drug screening or disease modelling,” said Anthony Atala, M.D., Editor of STEM CELLS Translational Medicine and director of the Wake Forest Institute for Regenerative Medicine.

Parkinson’s Disease Research – Ask the Stem Cell Expert, Dr. Xianmin Zeng

Dr. Xianmin Zeng, associate professor at the Buck Institute for Research on Aging answers your questions about Parkinson’s disease and stem cell research. Zeng has a CIRM research grant to develop a stem cell treatment for Parkinson’s disease.

Parkinson’s disease is a neurodegenerative disorder, which leads to tremors, slowness in movement, impaired balance, and stiffness. There is no cure for Parkinson’s. And although drugs can help reduce symptoms, they eventually lose their effectiveness. Zeng has developed methods for transforming those stem cells into dopamine-producing nerve cells, the same cells that are lost in Parkinson’s disease. The hope is that by transplanting these cells into the brain, they will replace the lost cells and restore function in the brain.

For more information about CIRM-funded stem cell research related to Parkinson’s research, see fact sheet.

Stem Cells Show Promise in Extending Transplanted Kidneys’ Survival Time

Can stem cells provide an answer to the perplexing question of how to ensure long-term survival of transplanted kidneys? The results of a new Phase 1 clinical trial say maybe so. Details of the trial, conducted by researchers at Leiden University Medical Center, The Netherlands, are published in the current issue of STEM CELLS Translational Medicine.

Kidney transplants have long been the treatment of choice for many patients with end-stage renal disease, and the short-term results are excellent. But unfortunately, the viability of these kidneys over time has not improved accordingly, often due to fibrosis, which is a scarring of the transplanted organ generally caused by the immune system rejecting it.

The LUMC team, led by Marlies E.J. Reinders, M.D, Ph.D., and Ton J. Rabelink, M.D., Ph.D., decided to test whether stem cells might keep fibrosis in check. They focused on mesenchymal stromal cells, a type of stem cell found throughout the body, including in bone marrow.

“Mesenchymal stromal cells (MSCs) are an interesting candidate due to their immunosuppressive and regenerative properties,” Dr. Reinders explained. “Of importance, no clinical studies have investigated their effects on rejection and fibrosis in organ transplantation.”

The team performed a safety and feasibility study in kidney transplant patients who, at four weeks or six months after transplant, were showing signs of rejection and/or an increase in fibrosis and wasting away of the kidney’s tubes (a condition called interstitial fibrosis/tubular atrophy. . In all, six patients received two intravenous MSC infusions of 1 million cells, collected from the patient’s own bone marrow and given one week apart. None of the patients had any sign of adverse, treatment-related side effects from the MSCs, although three developed infections associated with immune suppression.

Five of the patients had a specific decrease in immunity against the transplanted organ. In agreement, prior to the infusions, two of the patients had tubulitis — lesions that are a warning sign of organ rejection — which disappeared after the MSC treatment.

“These first clinical observations support the potential of stem cells as a novel cell therapy to prevent allograft rejection and interstitial fibrosis/tubular atrophy,” Dr. Rabelink noted, adding that long-term follow-up to better understand MSC-based treatment and to monitor unwanted side effects is needed, especially since transplant recipients are already at an increased risk for infection and malignancies.

“While the study wasn’t designed to test efficacy, these clinical observations are promising and suggestive of systemic immunosuppression,” said Anthony Atala, M.D., Editor of STEM CELLS Translational Medicine and director of the Wake Forest Institute for Regenerative Medicine.

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The full article, “Autologous bone marrow-derived mesenchymal stromal cells for the treatment of allograft rejection after renal transplantation: results of a phase I study,” can be accessed at http://stemcellstm.alphamedpress.org/content/early/2013/01/23/sctm.2012-0114.abstract.