Indian Transplant Newsletter Vol. II Issue NO.: 7 (Jan-Mar 2001)
Print ISSN 0972 - 1568

Stem Cell Transplantation



Print ISSN 0972 - 1568
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Research in stem cell is likely to benefit not only the field of transplantation but also many other fields including oncology. These summaries include a few highlights from this research fields.

 

An Alternative to Neural Stem Cell Transplantation

“Is it possible to include signals that will recruit stem cells right in the brain where they are without transplantation to make new neurons in the central cortex?”

 

This is the question that lead investigator Jeffrey Macklis, Ph D and colleagues from Harvard University Medical School, Boston asked. The findings from their experiments on mice were reported in the June 2000 issue of Nature and the answer was, “Yes, in small number”. Neural stem cells could be made to differentiate into mature neurons in regions of the cerebral cortex that normally did not undergo neurogenesis. A combination and sequence of molecular control signals direct stem cells to repair the brain from “the inside out”. These signals direct the cells to migrate to exactly the right location, to differentiate into the right kind of neurons and to survive.

 

The future is exciting but it is still a long way off from human application. The research team will be working first to uncover the combination and sequence of molecular control signals and then to manipulate the system with specific growth factors to try to increase the rate of new neuron production.

 

Macklis thinks that by increasing the number of stem cells or guiding them more efficiently, many more appropriate new neurons could be made. He also thinks that in the next decade, the neurons that are affected in spinal cord injury or ALS might get a clinical benefit from this approach. This is because a relatively small number of imperfectly, imprecisely wired neuron could make the difference between the lack of function altogether and some kind of function, imperfect through it may be.

 

However, treatment for diseases like Parkinson’s or Alzheimer’s is decades away because of the needs for absolute precision of the neuron wiring.

 

RESEARCH ON USE OF NEURAL STEM CELLS FOR RETINAL TRANSPLANTS

 

Researchers from the schepens eye research institute injected adult rat hippocampal neural stem cells into eyes of rats with retinal degeneration .The retina of 1,4 and 10 week old rats showed widespread incorporation of donor cells, while 18 week old recipients showed acceptance but  fewer cells .The cells were put into the vitreous and migrated into the retina .They not only appeared to take on the right  characteristics but also showed early signs of trying to connect the retina to the brain .The research could help people whose vision has been impaired  by retinal detachment ,macular degeneration ,glaucoma ,diabetic retinopathy as well as those with brain disorder (Alzheimer’s, Parkinson’s)and spinal injury .

 

Some of the interesting finding that came up during the study was that the transplant worked best when the retina was sick. In healthy retinas, the stem cells did not transfer into retinal cells, leave alone migrate to the retina .Also, the fact that since the rat retina is fully developed before the end of the third post natal week, the widespread incorporation seen at 4 and 10 weeks indicates that developmental maturity is not a barrier to the acceptance of neural stem cells by the diseased mammalian retina.

 

REVERSAL OF ADVANCED KIDNEY CANCER THROUGH STEM CELL TRANSPLANT POSSIBLE, ACCORDING TO STUDY

Metastatic renal cell cancer is highly resistant to chemotherapy but unlike other solid tumours is susceptible to attack by the body’s immune system. The use of drugs designed to boost immune function such as interleukin-2 and interferon –alpha has been beneficial  to some patients only .Taking their cue from the potent immune medicated anticancer  effects following allogeneic  stem cell transplantation in leukaemia  and lymphoma ,Richard Childs .MD  and his colleagues at the National Heart ,Lung and Blood Institute decided to try something similar in patients with treatment resistant renal cancer .The patients had stem cell transplants from  sibling donor and the response rates were encouraging .It was interesting to note that 6 of 10 patients who ultimately had a favourable response had initial evidence of tumour growth in first few transplant months. It was also noted that tumour regression did not occur until the immune system had been completely replaced by the donor cells and in most cases developed only after the withdrawal of cyclosporine .Patients who failed to completely replace  their immune system with donor cells or who had tumour growth ,following their transplants were given additional infusions of donor lymphocyte cells to promote anti-tumour activity .There was a flip side to stem cell transplantation, however 53% of the patients developed acute graft-versus-host disease (GVHD).

 

Two patients died due to transplant related complications, one from (GVHD) and another from bacterial sepsis. In addition the prolonged time required for the induction of an anti tumour effects with therapy would be of no help to patients with rapidly advancing metastatic disease.

 

Metastatic  cancer regressed in 10(53%)of the 19 patients treated in the phase 1/11 study -3 patients (16%)had a  complete response and 7(38%)had a partial response (New England journal of medicine –sep,14th,2000.In fact ,a few of the patients remained completely free of cancer more than 2 years  from the initiation of therapy .

Adult Stem Cells Transplants- Will They be The Answer to Transplant of Human Disease in The Future?

Embryonic stem cell transplants and possible treatment are considered to be the cornerstone in the treatment of many diseases because of their remarkable ability to differentiate into any kind of tissue. But researchers at karolinska Institute in Stockholm, Sweden have come up with some exciting findings involving stem cells from the brains of adult mice. They showed that these stem cells could be matured into heart, liver, muscle and other tissues and could make their way to appropriate body locations. Jonas Trisen, PhD  and his colleagues removed stem cells from the central nervous of adult  mice ,genetically engineered them to carry an easily traceable marker ,and injected them into mouse and chicken embryos .They found that the transplanted cells not only took up residence in the embryo’s developing brains and spinal cords but were also converted into a variety of other body tissues and organs .The conversion rate was only about 12% or less and the marked cells were not detected in many places, bone marrow  being one of them. However, other experiments in adult mice have shown that neural stem cells can differentiate into various blood cells.

 

A number of questions still need to be answered:

Can adult stem cells be used to grow new organs or to treat diabetes, Parkinson’s and Alzheimer’s? What was the nature of the signals that prompted the neural stem cells to become different types of tissues?

But the exciting part ,as Freisen  and his colleagues say is that all the combined research to date indicate that “stem cells in differentiate adult  tissues may be more similar than previously thought and perhaps in some cases have a developmental repertoire close to that of embryonic stem cells.”

 

EMBRYONIC CELLS TRANSPLANTS COULD HELP TREAT SPINAL CORD INJURIES, MULTIPLE SCLEROSIS


Embryonic cell transplantation techniques hold out hope for repair of damaged myelin sheaths in spinal cord injuries and multiple sclerosis.

 

After neural cells, John McDonald MD and colleagues at Washington university school of medicine in St. Louis, USA cultured embryonic stem cells and induced them to become precursors to oligodendrocyctes, the nerve cells responsible for producing myelin. These precursors were then transplanted into rats whose spinal cords had been chemically demyelinated. In a little over a week, large numbers of the transplanted cells had differentiated into mature oligodendrocytes and were forming myelin.

 


To cite : Shroff S. Stem Cell Transplantation. .
Available at:
https://www.itnnews.co.in/indian-transplant-newsletter/issue7/Stem-Cell-Transplantation-167.htm

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