Remarkable Stem Cell News From Shanghai

The 3rd Annual World Congress of Regenerative Medicine and Stem Cells 2010 in Shanghai last month (December) was the stem cell version of the Shanghai Exposition. Stem cell news on steroids, in other words. While China’s burgeoning research output was front and center, the rest of the world also showed up and put on display a vast array of clinical techniques, strategies and new research about the use of stem and progenitor cells (usually mesenchymal stem cells) in patients, at their bedside.

The range and variety of clinical presentations was more extensive than anything we’ve seen in the U.S. For this short article, we will describe and discuss the nerve and cartilage regeneration papers. Suffice it to say, the work being performed in places like Kuala Lampur, Malaysia, the United Arab Emirates, and France are changing medicine. All of these clinical activities are being performed under the regulatory structure of both the institution and the government. Because this is different (not better or worse, just different) than FDA rules, the manner and style in which these cells are being incorporated into orthopedic treatment plans is very encouraging.

In the United States, the occasional paper emerges that provides a hint at the coming stem cell revolution (for example Dr. S. Robert Rosbruch, Chief of Limb Lengthening and Complex Reconstruction Service at the Hospital for Special Surgery, used bone marrow derived stem cells to treat arthritic sub-talar ankle joint—“…this will change my practice, because when someone comes in, I’m going to think twice about offering just a routine sub-talar fusion, and really pose this [stem cell injection] as an option”). But at the Shanghai World Congress, the range of clinical information was extraordinarily extensive.

For our own New York Stem Cell Summit, we’ve invited some of the Shanghai presenters and it should deliver, we think, one of our best meetings yet.

Regenerating Articular Cartilage in the Knee

Dr. Khay-Yong Saw (Liverpool University School of Medicine 1979-1984, FRCS in Edinburgh 1989, Masters in Orthopaedic Surgery Liverpool University Medical School, founder and senior partner Kuala Lumpur Sports Medicine Centre) has changed his practice since incorporating stem cells to treat arthritic knees. His technique is interesting and blends several existing techniques with the application of autologous stem cells. While Dr. Saw did present his paper, in private conversations he described in great detail how he now incorporates stem cells in virtually every patient with chondral defects.

Dr. Khay-Yong SawDr. Saw is conducting an ongoing clinical trial to assess the results of a particular technique for treating chondral defects with a combination of sub-chondral drilling, hyaluronic acid (HA) and autologous, concentrated stem cells. Dr. Saw works closely with his hospital’s hematologist to obtain the stem cells.

Dr. Saw presented data for 180 patients with full thickness chondral defects. Each patient was treated with arthroscopic subchondral drilling (in a tighter formation than typical subchondral drilling). Following surgery, each patient was place on a continuous passive motion (CPM) machine two hours per day for a period of four weeks and was on partial weight bearing for the first six weeks.

Dr. Saw harvested blood from his patients and then concentrated the mesenchymal stem cells (autologous peripheral blood stem cells – PBSC) by using the process of apherisis one week after surgery. Dr. Saw collected and concentrated enough material to create 8 mls of harvested PBSC. He then combined the PBSC with 2 mls of HA and injected the stem cell cocktail into the operated knees of his patients one week after surgery.

The remainder of the harvested PBSC were divided into vials and cryopreserved for future injections.

In total, Dr. Saw injected each patient five times with PBSC + HA into the intra-articular capsule—one per week. Dr. Saw and his technicians took serial MRI scans and in five patients conducted a second look arthroscopy with chondral core biopsy. He followed his patients for up to 30 months.

Dr. Saw’s MRI scans showed that each patient’s subchondral bone healed and the chondral defect filled in—which is a strong indicator of articular cartilage regeneration. For those patients who had a second look arthroscopy with chondral core biopsies, Dr. Saw confirmed that each patient had grown articular cartilage with hyaline cartilage. Each patient in the study showed an improved IKDC score (International Knee Documentation Committee score is a standardized questionnaire which is used by patients to self-report the status of their knee).

In Arthroscopy, Vol 25, No 12 (December), 2009: pp 1391-1400, Dr. Saw wrote an article describing this same approach on a goat model. That study also demonstrated that this technique will regenerate articular cartilage in the knee.

For Dr. Saw, this approach has changed his practice. He is routinely treating chondral lesions using this technique—namely, with a single arthroscopic procedure followed by post-operative intra-articular injections of autologous stem cells combined with HA.

Femoral Head Treatment

In another paper, Dr. Dewei Zhao, professor in the Department of Orthopedics, Affiliated Ahongshan Hospital of Dalian University, China, presented data from using bone marrow mesenchymal stem cells (BMMSCs) to treat osteonecrosis of the femoral head (ONFH).

In this study Dr. Zhao randomly assigned 100 patients with early stage ONFH to BMMSC treatment or core decompression (CD). Each patient receiving the BMMSC treatment received 2×106 autologous subtrochanteric bone marrow derived and cultured BMMSCs.

Each patient’s radiographic stage of ONFH was measured according to Association Research Circulation Osseous classification, Harris hip score (HHS) and the osteonecrotic volume in the femoral head was assessed both preoperatively and post-operatively at 3, 6, 12 and 24 months.

How did the patients do? At 24 months 51 out of the 53 BMMSC-treated hips had their ONFH delayed or avoided entirely a femoral head collapse due to osteonecrosis. By contrast, of the 47 non-BMMSC treated hips (core decompression) 10 progressed to higher osteonecrotic stages and were treated with either vascularized bone grafting (n=5) or total hip replacement (n=5).

Treating Paralysis and Nerve Trauma

Probably the most dramatic presentation of the Shanghai meeting was Dr. Haluk Deda’s video presentation of his treatment of traumatic spine cord injuries. Dr. Deda treated nine patients with chronic complete spinal cord injury (SCI) impairment scale (AIS) grade A.

Dr. Haluk DedaIn his videos, Dr. Deda first demonstrated the complete nature of each patient’s paralysis. They were paralyzed.

Each patient was injected in the neck with autologous bone marrow derived progenitor cells.

The transplant protocols were approved by the hospital’s ethical board and all information and written consents about the patients were provided to the ministry of health after treatment.

Patients who were included in the test had only one single spinal cord lesion. All patients had injuries that were six months or older. No patients were included who’d had an anatomical transaction of the cord as confirmed with MRI or patients who required mechanical ventilation or had a preexisting serious medical condition.

Dr. Deda aspirated 100-150ml of bone marrow from the iliac crest of each patient and then sent the samples to Aastrom Biosciences in Michigan for further culturing. Dr. Deda performed a complete laminectomy one vertebra above the injured site and one vertebra below the injured site in order to provide sufficient access to the injured spinal cord.

Dr. Deda then located avascular and ‘safe’ areas for stem cell injection. 0.1 ml of stem cells were injected using a 21 gauge needle attached to a 1-ml syringe in multiple sections of the damaged spinal cord.

All nine patients completed the protocol with no adverse events. At three weeks each patient was reporting increased muscle strength, movement and sensation to ASIA grade B or C and the MRIs of some of the patients suggested nerve regeneration.

Most dramatically, Dr. Deda provided videos at three weeks, six months and 12 months showing the formerly paralyzed patients moving in swimming pools, lifting legs and arms and demonstrating back movement. One patient even returned to work, typing.

Dr. Deda showed each patient’s video in a sequence that started with the pre-operative demonstration of paralysis and then a progressive partial recovery from paralysis at three weeks, three months and so on. The visual impact of watching formerly paralyzed patients demonstrating movement was much more powerful than the statistical report. The audience of scientists and clinicians were audibly astonished at Dr. Deda’s report.

Certainly, Dr. Deda was careful to use patients who were younger and whose cord traumas were of a particular type. Still, Dr. Deda’s research showed clearly that autologous stem cells are a viable option for treating certain kinds of spinal cord injuries including those that result in paralysis.

Dr. Deda’s CV includes: Ankara University Medical School 1980, postdoctoral research fellow at Baylor College of Medicine, further postdoctoral research at University of London institute of Neurology, then Hanover Medical School, Nordstadt Hospital Department of Neurosurgery in Germany, then University of Arkansas in 1994, University of George Washington 1996 and full professor Ankara University. Creator of the Halman Neurtherapy Center in DHCC in United Arab Emirates in 2009.

New York Stem Cell Summit

In total there were about 260 presentations in Shanghai by researchers and clinicians from China, Japan, Korea, Vietnam, United Arab Emirates, Turkey, Norway, USA, Italy, Taiwan, Australia, Brazil, Malaysia, Canada, Belgium, Egypt, UK, France, Poland, Singapore, Portugal, Switzerland, Iran, Russia, Israel, Chile and the Netherlands.

While allograft stem cell products are the predominate commercial form of stem cell therapy in the United States, the rest of the world is rapidly adopting autologous (blood or bone marrow derived) stem cell therapies for a broad range of indications.

For more information regarding the quickly evolving world of stem cell therapies, we look forward to seeing you at the New York Stem Cell Summit scheduled for March 1, 2011 (www.stemcellsummit.com).