Dr. Ira Black

[paulsask]

Greetings

Dr. Young - Do you have current information regarding the work of Ira Black ?
I did a search only to come up with that stem cell/bone marrow story from August 2000.
Chris Reeve was quite excited, quoting the finding the equivelant of "inventing the wheel".
I remember the media hype over this discovery. The article states "researchers have successfully transformed stem cxells from bone marrow into functioning brain cells in BOTH rats and humans".
Sounded good - no rejection, not sure about procedure though.
Anyway, I haven't heard anything from him in 18 months. He's located in N.J and thought you may correspond with him fairly regularly.
What (if any) success since August 2000, has he had with these cells in humans ?
The cells transformed into functioning brain cells, but what types. Do we not need to see functioning neurons, astrocytes and oligodendrocytes ?
Please help me out here, as you so graciously do always.

Later......Paul

[Wise Young]

Paulsask, Ira Black's group was the first to report that bone marrow stem cells can produce neurons. However, they did not transplant the cells into the brain or spinal cord at the time. Please note that many laboratories have now reported that they can get bone marrow mesenchymal stem cells to form neurons. Ira Black's laboratory does want to transplant such cells to the spinal cord and have applied for funding to carry out the work. Wise.

[paulsask]

Greetings

Dr. Young, would this type of transplant be able to be carried out non invasively ?
Could this be done through injection ?
Is there alot of steps or time needed to first retrieve the cells, culture then back into the recipient ?
What kind of man hours would have to go into a 12 person study ?
What is your opinion on this type of procedure and is anything else (in your opinion) needed to promote the best results.

Thanks........Paul

[DA]

you meann he hasnt transplanted the cells in humans? right?
because i remember reading the cells were transplanted in rodents and the cells survived and formed a neural net.

[sinbad]

Mending broken hearts

Simple cell implants could undo the damage wrought by heart attacks

REPAIRING a damaged heart suddenly seems possible. Two teams of scientists report that stem cells can fix some of the damage caused by heart attacks. The techniques could be tested in people as early as next year.

The havoc caused by a heart attack comes in two stages. Minutes after a coronary artery is blocked, heart muscle cells begin to suffer from the lack of oxygen and nutrients. If doctors don't clear the blockage immediately, the cells die and the heart is permanently damaged.

Days or weeks later, the heart compensates by remodelling, enlarging the muscle cells so they can pump harder. But this valiant effort is often futile. The lowered blood supply can't support the increased effort of the cells and causes more of them to die, thinning and weakening the heart muscle.

Now a team led by Piero Anversa of New York Medical College in Valhalla has shown that stem cellsundifferentiated cells that can give rise to many specialised typescan repair some of the immediate damage that is caused by heart attacks.

The researchers first induced heart attacks in mice. A few hours later, they injected stem cells taken from mouse bone marrow directly into the heart wall.

After nine days, the transplanted cells had regenerated 68 per cent of the damaged muscle and increased blood flow. The function of the heart improved by 33 per cent. We saw that and we were screaming like kids, says Anversa. In a few months, his team will start experiments in monkeys, he says. The technique may be tested on people within three years.

Another team led by Silviu Itescu at Columbia-Presbyterian Medical Center in New York has used stem cells to restore the heart's blood supply and prevent further damage after a heart attack. Even if you lose just a bit of your heart in the initial attack, the damage extends and you end up in heart failure again, says Itescu.

He and his colleagues purified human angioblastsbone marrow stem cells that form blood vessels during the development of the embryo. These cells were injected into rats two days after heart attacks had been induced.

The cells created new blood vessels in the damaged area and caused nearby blood vessels to branch, improving heart function by 26 per cent. Because Itescu can already isolate these cells from people, he says his team may be able to start clinical trials within a year.

Other researchers are cautiously optimistic. There have been 20 years of disappointing experiments trying to replace cells in the heart, says Mark Sussman, a cardiovascular molecular biologist at The Children's Hospital and Research Foundation in Cincinnati, Ohio. This new work looks very promising, but we need to understand why it is working and if we can get even better results.

MY CONCLUSION
1)Although the hearth cure fundunding 100x times more than scı reserach ,unfortunately they havent been succesfulgiven below

a)20 years of dissapointing experiments

b)it takes 4 years to test it.

c)please remember that %100 of millionires funds these research billions bececause of the heart attack fear.

2)Any more nobody must attack the Neuroscientist after reading my post. 2002 will be the year of motivating scientist.

3)Lets assume that there is answer of the SCI on the other universe. And lets assume that they send the formula of the scı repair molecule (written forms of the cure ) . Please remember that it takes 15 years to reach the message to us. this is the case occured once 1945(ı thing) but this mesaj never understood clearly.

4)Scientist and the science is solely rescue of us. Never forget this. I hope that science will shape our future. Science will be the 1.st powerfull policy ın this earth.
best regards

[Wise Young]

Paulsask, the original work by Ira Black's group reported that they saw cells that expressed markers for neurons in cultures of bone marrow stem cells. They were beginning to characterize these cells physiologically in culture. They used a chemical to stimulate the appearance of these cells. To my knowledge, Ira Black's group had not transplanted bone marrow cells to injured spinal cords.

However, other groups have reported that bone marrow stem cells can be injected intravascularly and that the injected cells will end up in the brain and spinal cord. To my knowledge, none of the studies have shown definitely that bone marrow stem cells will form neurons in injured spinal cords. Apparently, however, bone marrow stem cells can form other kinds of cells. One recent study suggested that bone marrow cells will remyelinate the spinal cord. See Sasaki, et al. (2001) in Research Forum

As you may have read in another topic, Paulo Peri reported that one Italian group has transplanted bone marrow stem cell autografts to 3 patients with spinal cord injury in Italy. I am of course anxiously awaiting word of the outcome of this study. I do want to point out that Italy is ahead of the U.S. in some respect when it comes to clinical experience with bone marrow transplants (see below).

Regarding what would be required to get such a study going in the United States, what one needs is a center that has a scientist who has substantial experience isolating bone marrow stem cells (also called mesenchymal stem cells) and an enthusiastic group of neurosurgeons who are willing to spend the time and effort setting up a protocol to transplant such cells to patients. I think that there are several centers in the United States with such expertise and are considering such procedures. The places that may do so include the groups at the Washington University in St. Louis, University of Louisville, University of Kentucky, Yale University, Hahneman University in Philadelphia, Stanford University, Washington University, and many others.

Wise.

• Comi G, Kappos L, Clanet M, Ebers G, Fassas A, Fazekas F, Filippi M, Hartung HP, Hertenstein B, Karussis D, Martino G, Tyndall A and van der Meche FG (2000). Guidelines for autologous blood and marrow stem cell transplantation in multiple sclerosis: a consensus report written on behalf of the European Group for Blood and Marrow Transplantation and the European Charcot Foundation. BMT-MS Study Group. J Neurol. 247 (5): 376-82. Summary: Recent reports suggest the possible beneficial effects of haemopoietic stem cell transplantation (HSCT) in autoimmune diseases such as multiple sclerosis (MS). The definition of the risk/benefit ratio for such a treatment is perceived as a major issue for the neurological community worldwide. The First Consensus Conference on Bone Marrow Transplantation in Patients with Multiple Sclerosis was held in Milan, Italy on 21 February 1998. Participants from 16 European, North American, and South American countries discussed the guidelines for performing HSCT in MS. This conference was organized in order to: (a) define criteria for patient selection; (b) define transplantation procedures to maximize efficacy of the treatment and minimize its toxicity; (c) standardize patient outcome evaluation; and (d) establish an international working group to evaluate the efficacy and safety of HSCT in MS and to study the immunological changes related to HSCT in MS patients. During the meeting in Milan agreement was reached on: (a) the preparation and distribution of a consensus report on HSCT in MS and (b) the design of an open trial for an initial assessment of the safety and efficacy of HSCT in MS. The consensus reached during the meeting and the design of the clinical trial are summarized in this contribution. Multiple Sclerosis Centre, San Raffaele Scientific Institute, Milan, Italy. g.comi@hsr.it

• Raiola AM, Van Lint MT, Lamparelli T, Gualandi F, Benvenuto F, Figari O, Mordini N, Berisso G, Bregante S, Frassoni F and Bacigalupo A (2000). Bone marrow transplantation for paroxysmal nocturnal hemoglobinuria. Haematologica. 85 (1): 59-62. Summary: BACKGROUND AND OBJECTIVE: Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal disease of the hemopoietic stem cell (HSC) characterized by intravascular hemolysis and increased risk of venous thrombosis. There are different therapeutic approaches for PNH which do not cure the disease, but can decrease its complications. Allogeneic bone marrow transplantation (BMT) may cure PNH. We reports here our experience of seven PNH patients who underwent allogeneic BMT. DESIGN AND METHODS: Between January 1991 and January 1999 seven patients with PNH, aged 23 to 37, were transplanted with unmanipulated bone marrow from HLA identical siblings. Median time from diagnosis to BMT was 2.5 years (range: 1-16). All patients were transfusion-dependent and had received various treatments before BMT: steroids, vitamins, cyclosporin A (CyA), growth factors. One patient had also been treated with anti-thymocyte globulin. One patient was HbsAg positive and one anti-HCV positive. At the time of BMT the median value of hemoglobin (Hb) was 9 g/dL (range 6.5-11), white blood cells 5&10(9)/L (range: 2.9-7.7), platelets 97&10(9)/L (range: 31-355), LDH: 2726 U/L. The conditioning regimen was cyclophosphamide (160 mg/kg) and busulfan (10-14 mg/kg), followed by unmanipulated bone marrow (median of 5&10(8) cells/kg) and CyA (+MTX in two patients) for prophylaxis of graft-versus-host disease (GvHD). RESULTS: All seven patients are alive, full chimeras, with complete hematologic recovery and no evidence of PNH, at a median follow up of 51 months post-BMT (6-103). Time to achieve a granulocyte count of 0.5&10(9)/L, platelets 30&10(9)/L and Hb 10 g/dL was respectively 16, 19 and 22 days. Acute GvHD was limited or mild in six patients, and severe in one. Chronic GvHD was extensive in two patients. INTERPRETATION AND CONCLUSIONS: This study confirms that HLA identical sibling BMT is an effective therapeutic option for PNH, also in the hemolytic phase of the disease: it also suggests that HBV and HCV infections are not an absolute contraindication.
Dipartimento di Ematologia, Ospedale San Martino, largo R. Benzi 10, 16132 Genoa, Italy. apbacigalupo@smartino.ge.it.

[This message was edited by Wise Young on January 06, 2002 at 09:06 AM.]

[Joe B]

Why are these discussions only considering bone marrow stem cell transplants?

I know that the NIH routinely stimulates the bone marrow to produce excessively large numbers of stem cells and then transplants them intravascularly. The key reason for doing this is that results show that IV infusion results in better transplants. This is the method they use for treating several forms of cancer.

Why wouldn't this method also work better than bone marrow transplantation which is harder on the donor and the recipient.

Dr. Young, why isn't NIH included in your list of centers capable performing such a transplant? I know they are fixated on cancer and HIV but sparing a few docs and bucks to try transplanting stem cells shouldn't be tooo hard as they already have the eqpt, staff and training.

I often do not understand why researchers cant/dont perform related research. I suppose it has to do with funding and grants. If you have a $100,000 grant for cancer you probably dont want to get caught spending $10,000 of it on SCI. You probably also dont have enough budget to take the 10k from your proposed cancer research.

Looks like there may be a need for research that is multifocused

Joe B

[Wise Young]

Joe B,

We are getting a little ahead of ourselves. There is as yet no evidence, except for one recently published paper, that bone marrow stem cells improve neurological recovery in any animal model. That recent published paper dealt with x-irradiated demyelination.

On the other hand, there is some animal studies suggesting that stem cells (although not from fetal or embryo sources) will improve function in transgenic mice with amyotrophic lateral sclerosis. That is why they are going ahead in Italy to use bone marrow stem cells to treat patients.

In order to get NIH funding, you have to show some rationale, some promising result in animal studies, or some theoretical reason why a therapy would work. Otherwise, you will not get funding. On the other hand, I was pointing out that should the animal results warrant a clinical trial, there are numerous institutions that are poised to go with such studies, including NIH as you mentioned.

Wise.

[sinbad]

Subcutaneous Polyethylene Glycol Promotes Recovery After Experimental Spinal Cord Injury

NEW YORK (Reuters Health) Dec 28 - In an animal model of spinal cord injury, rapid recovery of somatosensory evoked potential conduction and the cutaneous trunci muscle reflex occurs after subcutaneous administration of polyethylene glycol.

Drs. Richard B. Borgens and Debra Bohnert from Purdue University, West Lafayette, Indiana, induced crushing spinal cord injuries in 20 adult guinea pigs under anesthesia. Ten guinea pigs received a single subcutaneous injection of polyethylene glycol while the remaining animals formed a control group.

The researchers recorded neurologic status at 1 day, 1 week, 2 weeks, and 4 weeks after injury, according to their report in the December 15th issue of the Journal of Neuroscience Research.

During 1 month of observation, all the animals that received polyethylene glycol recovered somatosensory evoked potential conduction while none of the control animals did so (p = 0.001), Drs. Borgens and Bohnert found.

Cutaneous trunci muscle reflex was restored within 24 hours in three of the guinea pigs that received polyethylene glycol. Three more animals had restored reflex within 1 week, and another animal by the second week. None of the control animals had spontaneous cutaneous trunci muscle reflex recovery during the month, the investigators note.

"These data suggest that parenterally administered polyethylene glycol may be a novel treatment for not only spinal cord injury, but head injury and stroke as well," Drs. Borgens and Bohnert conclude. "This leads us to believe that polyethylene (and related polymers) may indeed be a promising treatment for some types of severe neurotrauma, where administration through the IV fluids might even be initiated at the site of emergency medical care."

J Neurosci Res 2001;66:1179-1186.

[sinbad]

Human heart can repair itself

Study finds new evidence of heart's regenerative power DOCTORS HAVE long assumed that damage from a heart attack or other ailment is irreversible and that the heart cannot regenerate tissue the way other organs can. But that belief has been shaken by recent research.
A team of American and Italian researchers demonstrated last year that heart muscle cells multiply after a heart attack. Now they have shown in a study published in this week's New England Journal of Medicine that in heart transplant patients, primitive cells from the patient travel to the new heart and grow new muscle and blood vessels.

CROSS-GENDER TRANSPLANTS
The researchers studied men who received transplanted hearts from women, and discovered male cells in the donated female hearts.
Discovering techniques to help the heart reverse heart disease and high blood pressure, "which were previously only pipe dreams, are now realistic goals that may soon be within reach," said Journal editors Drs. Robert Schwartz and Gregory Curfman.
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"There have been hints from animal studies that the cells could migrate before, but this is the first demonstration in a human that it is actually possible," said John Fakunding of the National Heart, Lung and Blood Institute, which helped pay for the study.
The researchers found that heart muscle and blood vessels grew rapidly in the new hearts after transplant. They calculated that as much as one-fifth of the donor heart had been rebuilt by the recipient's own cells.
"Clearly this shows that the heart has the ability to regenerate," said Dr. Roberto Bolli of the University of Louisville, who wrote an accompanying editorial. "It could be a milestone discovery if we learn how to exploit
this phenomenon for therapeutic purposes to regenerate heart muscle in patients with heart failure."
The researchers looked for the male Y chromosome in eight female hearts that were transplanted into men. After the heart recipients died, tissue samples were taken from each donor heart and from remnants of the old heart not removed during transplant surgery. The researchers found cells throughout the female heart that contained a Y chromosome. In some samples from the heart, more than 45 percent of the cells carried the Y chromosome.
It is unclear whether those cells came from remnants of the old male heart and migrated to the new one, or whether they were originally highly-versatile stem cells from the men's bone marrow and moved to the heart in an attempt to repair the damage from the heart surgery.
Many of the male cells that had found a home in the transplanted heart had characteristics of stem cells.
Even in the one patient who died four days after his transplant, the researchers found plenty of evidence in his heart that Y-containing cells had moved in and started work.
The speed and degree to which the cells of the host worked to repair and remodel the new heart "are surprising, revealing heretofore unknown aspects of cardiac biology," Bolli said.

SEARCH FOR CARDIAC STEM CELLS
"We have the first strong suggestions that the heart has primitive cells - meaning cardiac stem cells - which could be used in the future to repair the heart," said Dr. Piero Anversa, who led the researchers at New York Medical College in Valhalla, N.Y., and the University of Udine and the University of Parma in Italy. Stem cells are master cells that transform themselves into certain types of tissue, such as muscle, skin or bone. Doctors believe stem cells could one day be used to replace or fix failing organs.
Anversa said he and his colleagues are working to identify whether a cardiac stem cell exists and whether it can be manipulated to promote heart repair. "This is the work that we will be doing for the next couple of years," he said.
In the meantime, Anversa said his belief that the heart can repair itself is slowly gaining acceptance. "I think it is going to be more and more difficult to challenge us." he said.

The Associated Press and Reuters contributed to this report.