Stem-cell therapy in medicine-how far we came and what we can expect?

Apollo Medicine 2012 MarchReview Article

Volume 9, Number 1; pp. 41–43

© 2012, Indraprastha Medical Corporation Ltd

Stem-cell therapy in medicine—how far we came and what we can expect?

AVS Suresh**Consultant, Medical Oncologist and Hematologist, Apollo Cancer Hospitals, Apollo Health City, Jubili Hills, Hyderabad, India.

ABSTRACT

The name ‘stem-cell’ is making the news in recent times both for good and not. The current articles tries to give a snap shot of the scientific and clinical picture of stem-cells in medicine as of today and discuss what it have to offer in the to the mankind. The article discusses the characters and types of stem-cells, their current indication in therapeutics (both established and upcoming), as well as their use in research. It also gives a brief overview of the current laws guiding its use in clinical practice and the various cultural beliefs associated with the use of same.

Keywords: Cancer, ethics, regulatory, stem-cell

Correspondence: Dr. AVS Suresh, E-mail: sureshattili@yahoo.comdoi: 10.1016/S0976-0016(12)60119-7

INTRODUCTION

The name ‘stem-cell’ is making the news in recent times both for good and not. This article tries to give a snap shot of the scientific and clinical picture of stem-cells in medi-cine as of today and discuss what it has to offer to the mankind.

What are They?

Stem-cells are a population of undifferentiated cells which are able• to divide for indefinite period,• to self-renew, • to generate a functional progeny of highly specialized

cells.1

These cells can be present anywhere in the body and divide in case of need. According to the capability of dif-ferentiation, they were named1:• Totipotent (fertilized egg)—which can form all cell lines

including the placenta.• Pluripotent (embryonic cell)—they can form most of the

cell lines except the placenta.• Multipotent (e.g., hematopoietic)—they have limited

capacity to form one committed cell line such as blood cells, skin, neurons, myocytes, and endothelial cells.

History

Although, the concept of stem-cells is present for a long-time, the therapeutic use of the same was first demonstrated in mouse, where the team used it as the radiation protection phenomenon (mid-1950s), and it went on for testing in the dog. For the first time, it was done successfully in the humans by E. Donnall Thomes, which is the beginning of the modern era of hematopoietic stem-cell transplantation (HSCT).2

PRESENT INDICATIONS

Although, it was tested in many other indications, it was successful only in the hematological conditions just because of the fact that ‘the functionality’ of the progeny does not require integration with surroundings. Hence, the ‘stem-cell’ became synonymous with ‘bone marrow’ in the com-mon physician language. The other therapeutic areas such as ‘neurodegenerative disorders’3 though we are successful in transferring the cells into the mature cells like neurons, the major challenge is that we could not integrate them with the existing system thereby not meeting the definition of ‘ideally functional progeny’ despite the newly formed neu-ron being able to perform its function in isolation. Similar is the case with cardiomyopathies,4 where though the function

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42 Apollo Medicine 2012 March; Vol. 9, No. 1 Suresh

© 2012, Indraprastha Medical Corporation Ltd

(contractility) of the heart improved partially, the ‘perfect goal’ of normalization is still far from reality.5,6 However, the results of the same in peripheral vascular disease is promis-ing with a significant improvement in granulation tissue quality and it takes shorter time for recovery.7

HEMATOPOIETIC STEM-CELL

TRANSPLANTATION

The results of hematopoietic stem-cell transplant are quite mature with an experience of more than few million transplants happening across the globe so far. To summa-rize what we do in autologous transplant, we first make sure that there is no evidence of disease in the blood or bone marrow and give very high doses of chemotherapy after collecting stem-cells. The main advantage is we can deliver supraclinical doses of chemotherapeutic agents thereby hoping for longer disease-free life. Although transplant-related mortality (TRM) is lowest with autos (< 5%), the relapse rates are higher depending on the disease mainly due to the absence of graft versus tumor effect.

In allogeneic transplant, we give some ‘conditioning’ regimen ranging from various chemotherapy, radiotherapy, and immunotherapy combinations, so as to• make some space for the transplanted stem-cells

(controversial),• achieve immunosuppression, • eradicate the disease.

This will be followed by transplantation of donor stem-cells to the recipient which will be human leukocyte anti-gens (HLA)-matched (give a score of 3–6/6 and based on the degree they called mismatch, haplo match, and full match). This will be followed by transferring the patient to a clean room and allow the homing of transplanted stem-cells, and managing the complications like graft-versus-host disease during the recovery phase.1

Laws Governing Stem-cell Use

The controversy that testing on embryos is looked as ‘re-doing the God’, which is not completely wrong,8,9 has attracted a lot of attention both scientifically, culturally, and ethnically and since then there are some fixed guidelines in each country and in India too the Indian Council of Medical Research (ICMR) came up with guidelines to follow for the stem-cell research which can be accessed through www.icmr.nic.in/stem_cell/stem_cell_guidelines.pdf.

Sources of Stem-cells

Once upon a time, bone marrow was considered as the only source of stem-cells, extracting which was a tiresome job, which required general anesthesia and multiple punctures. The next major step in harvesting the stem-cells is the invention of ‘growth factors’ and ‘cell separator’, where it is now possible to extract them by giving few subcutaneous injections, thereby mobilizing stem-cells into circulation and collecting the same via a simple phlebotomy. This research also suggested that we can de-differentiate some cells to more immature cells like committed stem-cells → multipotent → pluripotent. And under given circumstances to re-differentiate to the cell line of our choice. For exam-ple, we can collect stem-cells from various sources like skin, and by multistep manipulation we can make a neuron or cardiac myocyte. Hence, it is not an exaggeration if we state that it is now possible to make the cell of our choice if we have a single cell line, which need not necessarily be the same line of what we want to make.10 However, still the conventional sources which are therapeutically used are as follows:• Bone marrow• Peripheral blood• Umbilical cord blood• Fetus liver.

The choice of graft is based on disease type, patient con-dition, donor compatibility, and health. Based on whether we are getting from the same patient or other patient, they can be further classified into• Allogeneic: from another person• Syngeneic: from an identical twin• Autologous: from the same patient.

How to Identify Ideal Stem-cell

There are some markers in the laboratory for us to identify the ideal stem-cell-like expression of CD34, CD133, Lin-C-kit (CD117), and breast cancer resistance protein (BCRP).

CONCLUSION

With so much advancements happening in the stem-cell sci-ence and the indications expanding so fast, the techniques for its storage also equally developed, and it is now possible to store them for up to 20 years at −140°C. With the realiza-tion that umbilical cord is one of the best sources of stem-cells, the cord blood banking is now becoming a standard

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Stem-cell therapy in medicine—how far we came and what we can expect? Review Article 43

© 2012, Indraprastha Medical Corporation Ltd

in most parts of the world, not only to meet unexpected adversities of the child, but also to donate for the needy people and help the cause of stem-cell research. If we progress the way we are now, it is possible to give some permanent solutions for the so-called ‘nothing much to do’ health con-ditions like storage disorders, neurodegenerative disorders, and cardiomyopathies. The ‘hope is real’ and will be.

REFERENCES

1. Stem Cell Basics. Accessed via http://stemcells.nih.gov/info/basics/

2. Siegel A. Locating Convergence: Ethics, Public Policy, and Human Stem Cell Research, in the Stem Cell Controversy Ruse M, Pynes C, eds. Prometheus Books 2003.

3. Lindvall O, Kokaia Z. Stem cells in human neurodegenerative disorders—time for clinical translation? J Clin Invest 2010;120:29–40.

4. Bolli R, Chugh AR, D’Amario D. Cardiac stem cells in patients with ischaemic cardiomyopathy (SCIPIO): initial results of a randomised phase 1 trial. Lancet 2011;378:1847–57 [Epub 2011 Nov 14].

5. Little, Melissa, Hall W, Orlandi A. Delivering on the promise of human stem-cell research. What are the real barriers? EMBO Reports 2006;7:1188–92.

6. Gennero L, Mortimer P, Sperber K, Carloni G, Ponzetoo A. Stem cells: an alternative to organ transplantation in chronic, degenerative and infectious diseases? New Microbia 2006;29:151–67.

7. Bernardi S, Severini GM, Zauli G, Secchiero P. Cell-based therapies for diabetic complications. Exp Diabetes Res 2012;2012:872504 [Epub 2011 Jun 9].

8. Dresser R. Ethical issues in embryonic stem cell research. JAMA 2001;285:1439–40.

9. Becoming Immortal: Combining Cloning and Cell Therapy. Stanley Shostak; State University of New York 2002.

10. Cai S, Fu X, Sheng Z. Dedifferentiation: a new approach in stem cell research. BioScience 2007;57:655–62.

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