Stem cell therapy

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As a stem cell therapy treatment methods are referred to, in which stem cells are used. It has been used for many years in the treatment of various cancers , such as leukemia . These indications are described under the heading stem cell transplantation .

In these therapies, either the body's own hematopoietic stem cells or those from a donor are used for adoptive cell transfer . These multipotent blood stem cells, from which colonies of both white and red blood cells could be grown, were discovered in 1963 by Canadian scientists James Till , Ernest McCulloch and Louis Siminovitch . A few years earlier, the first bone marrow transplant was carried out in 1957 .

Since the 1990s, however, many more stem cells have been discovered, isolated, and characterized. To date, it has not been sufficiently clarified how the individual types of stem cells are connected and what biological potential they have. In the last few years, however, many discoveries have been made in this field, and biomedicine has opened up entirely new and promising fields in medical research.

General information on the therapeutic use of stem cells

human stem cells (above) and nerve cells differentiated from them in vitro

Stem cells can be isolated from embryonic ( prenatal ) tissue on the one hand and from adult ( postnatal ) tissue on the other . Embryonic stem cells are pluripotent , while adult stem cells presumably have a more limited differentiation potential. In general, the more advanced the stage of development of an organism, the lower the rate of division and the more limited the differentiation potential of the stem cells isolated from it. A high division rate would be important in order to have enough cells available for a therapy; a broad differentiation potential allows more treatment options.

A large part of the scientific studies on stem cells is carried out in vitro , i.e. with isolated stem cells cultivated in special nutrient media, or in vivo on test animals. Research is currently still dealing with fundamental questions, such as how these stem cells can be made to differentiate into very specific cell types in order to replace damaged tissue with them (cell replacement therapy). Other questions include migration behavior (the migration of cells to a specific location after successful transplantation ) or the formation of cell-protective factors ( cytokines , growth factors ) that are supposed to protect existing functional tissue from further destruction or even regenerate it ( regenerative medicine ).

Prenatal stem cells and therapeutic options

Embryonic stem cells have raised many ethical but also scientific concerns in recent years (→ embryonic stem cells ). Although they can be differentiated into almost all body cells (and thus could be used universally), their use is limited for the time being. This is due not least to their high rate of cell division, which is desirable for the cells to multiply, but at the same time represents an increased risk of the development of malignant tumors .

Stem cells that originate in a later stage of the fetus have a lower rate of division and a more limited potential for differentiation (depending on which area of ​​the fetus they were isolated from). In animal experiments, however, they led to the improvement of some clinical pictures and have already been tested on over 300 Parkinson's patients worldwide with some success, even if they are initially hardly used due to serious side effects and ethical concerns.

Stem cells from the uterine fluid have only recently been isolated. They are cells, mostly of epithelial origin, which detach themselves from the fetus during the development of the fetus. They can be obtained directly from the amniotic fluid and can be propagated in vitro .

Other, actually “early adult” ( postnatal ), stem cells can be isolated from the umbilical cord blood . They have been known for a long time and their use is currently being intensively researched (→ umbilical cord blood stem cells ).

Ethical concerns similar to those with embryonic stem cells would be avoided if these two cells were used, and since they are taken from the organism at a relatively early stage, they presumably have broad potential for differentiation.

The only two patient trials approved by the US Food and Drug Administration (FDA) have been running since April 2011 . Here older patients with dry macular degeneration (AMD) and younger patients with Stargardt's disease are treated with cells of the retinal pigment epithelium (RPE), ie 50–200,000 RPE cells are injected into the retina of one eye. These cells are obtained from embryonic stem cells without destroying an embryo (patented blastomere technology, similar to PGD diagnostics). Over 40 patients have now been treated in four eye clinics in the USA and two in the UK. A peer-reviewed article was published in The Lancet in October 2014 . According to him, the majority of patients had significant improvements in vision. This has led the FDA to approve a series of tests for younger patients as well. In principle, such experiments begin with older patients who already have an advanced disease of their visual performance. The primary concern is the safe use of the therapy.

Adult stem cells and therapy options

Neural stem cells, which are mainly isolated from the ventricular walls of the brain, can be differentiated into the three main types of neural cells ( nerve cells as well as astro- and oligodendroglial cells ). In principle, they would be suitable for treating neurodegenerative diseases , as they can theoretically replace nerve tissue. However, these cells are only present in the organism to a small extent and have a low rate of division. In addition, the central nervous system is an extremely complex tissue that makes tissue replacement very difficult.

Stem cells from the mesenchyme are v. a. Obtained from the bone marrow, even from that of older people, have a high rate of division and can primarily differentiate into tissue cells of mesenchymal origin (bones, cartilage, tendons, muscles, connective tissue, blood cells). They could therefore be used directly for the treatment of degenerative diseases in these organs. Since around the year 2000, more and more attempts have been made to differentiate these cells into cell types of other tissues ( transdifferentiation ), such as nerve cells , liver cells , epithelial cells , β cells and renal tubule cells , in order to identify their therapeutic potential for corresponding diseases in this area to investigate. Studies of bone regeneration using mesenchymal stem cells from umbilical cord blood are showing initial success.

Other adult stem cells can be found in muscles, liver, fat and bone tissue and many more. Their possible uses are also being examined. A general advantage of adult stem cells is that they could, in principle , be transplanted autologously ; H. the donor z. B. mesenchymal stem cells would, after appropriate pretreatment of the cells, also be their recipient (e.g. in the context of a neurodegenerative disease).

Possible risks and side effects of stem cell therapy

The experiments described above are therapeutically promising , depending on the disease model (for example, whether it is local organic damage or rather a systemic disease ). Not least because of this, more and more patients with a fatal illness or irreparable damage, such as after paraplegia , are being subjected to such an “experimental” treatment, the outcome of which is, however, completely uncertain.

At present, stem cells are only transplanted in a few cases (see introduction). These therapies have been tested in controlled clinical studies over many years or even decades and were only used because they were effective

  1. proven effective and
  2. the therapeutic benefit outweighs the possible side effects .

For example, there are numerous animal studies on mesenchymal stem cells , which were discovered only a few years ago, and the results of these studies support the effectiveness of the treatment. Their effectiveness in humans is currently being investigated as part of a clinical study so that these cells could be approved as medicinal products for advanced therapies .

Application of stem cell therapy in competitive sports

In the case of muscle injuries in top-class sport, great importance is attached to recovery as quickly as possible, as the failure of individual athletes / players is associated with considerable disadvantages - and top-level sport is associated with major health risks anyway. While the use of stem cell therapy in Germany is still far behind (and thus, according to UEFA surveys, the injury duration for players in European club competitions is longer than average), this is e.g. B. widespread in top-class sport in Spain. Pep Guardiola has therefore also requested other treatment methods from FC Bayern . Stem cell therapy seems to have had the shortest regeneration times after muscle injuries so far, when combined with hyperbaric therapy . The recovery times after muscle injuries were reduced by more than a third for South African top rugby players.

Risks of "stem cell tourism"

Many patients with a serious, fatal illness hope for successful treatment in private clinics, which promise a cure through an often risky type of application (e.g. injection into the brain) of scientifically undefined stem cells. Most of these clinics are located in countries that have less stringent requirements for experimental therapies on humans (for example in China, Ukraine, Turkey), but also in Western Europe (e.g. in the Netherlands). By paying large sums of money for a treatment (for example € 20,000–50,000 per treatment), patients often bring themselves close to financial ruin, even though the prospect of success is small or unpredictable. To date, there are no well-founded reports that a person has completely recovered from such stem cell therapy, nor has the course of the disease been significantly slowed down. The treating private clinics usually do not collect or publish any scientifically valid information that would provide information about the effectiveness of the treatment. Accordingly, there are hardly any studies on possible side effects, especially with systemic administration of the cells. In isolated cases where it was possible to observe the patients before and after the transplantation, side effects were observed ( e.g. meningitis after transplantation of a mixture of fetal brain cells into the spinal cord).

In 2009, a case was reported of a boy with Louis Bar Syndrome who had been treated in Russia with injections of a mixture of fetal brain cells (which may contain stem cells) into the brain and spinal cord. From this mixture of cells, several tumors subsequently developed in the cerebellum and spinal cord.

The International Society for Stem Cell Research has created a patient brochure in order to protect patients from dubious, possibly damaging stem cell treatments or to educate them about them .

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  2. ^ AD Ho, K. Beyreuther: Fascinating all-rounders - "raw material" stem cells? In: Ruperto Carola. No. 3, 2001, Heidelberg University Hospital
  3. ^ IOP eV (Berlin): The history of transplantation ( Memento from June 27, 2009 in the Internet Archive )
  4. ↑ Patrizia Bossolasco, Tiziana Montemurro, Lidia Cova, Stefano Zangrossi, Cinzia Calzarossa, Simona Buiatiotis, Davide Soligo, Silvano Bosari, Vincenzo Silani, Giorgio Lambertenghi Deliliers, Paolo cells Rebulla, Lorenza Lazzari: Molecular cells and their different phenotypic fluidization of human amniotic fluidization potential . In: Cell Research . tape 16 , no. 4 , 2006, ISSN  1001-0602 , p. 329-336 , doi : 10.1038 / sj.cr.7310043 , PMID 16617328 .
  5. ↑ ongoing-clinical-trials ( memento of the original from March 31, 2015 in the Internet Archive ) Info: The archive link was automatically inserted and not yet checked. Please check the original and archive link according to the instructions and then remove this notice. . OCATA Therapeutics website. Retrieved March 28, 2015. @1@ 2Template: Webachiv / IABot / www.ocata.com
  6. ↑ Steven D. Schwartz et al .: Human embryonic stem cell-derived retinal pigment epithelium in patients with age-related macular degeneration and Stargardt's macular dystrophy: follow-up of two open-label phase 1/2 studies. In: The Lancet. Volume 385, No. 9967, 2015, pp. 509-516, doi: 10.1016 / S0140-6736 (14) 61376-3 .
  7. ↑ M. Jäger, M. Sager, A. Knipper, Ö. Degistirici, J. Fischer: In vitro and in vivo bone regeneration using mesenchymal stem cells from umbilical cord blood . In: The orthopedist . tape 33 , no. December 12 , 2004, ISSN  0085-4530 , p. 1361–1372 , doi : 10.1007 / s00132-004-0737-x ( springer.com [accessed September 19, 2018]).
  8. ↑ Alan Trounson, Rahul G. Thakar, Geoff Lomax, Don Gibbons: Clinical trials for stem cell therapies . In: BMC Medicine . tape 9 , 2011, p. 52 , doi : 10.1186 / 1741-7015-9-52 , PMID 21569277 .
  9. ↑ Siegmund Lang, Gero Brockhoff, Boyko Gueorguiev, Michaela Huber, Johannes Zellner: Modification of centrifugation to reduce the number of leukocytes in platelet-rich plasma and the effect on the proliferation of autologous mesenchymal stem cells . In: Sports Orthopedics and Traumatology Sports Orthopedics - Sports Traumatology . tape 32 , no. 2 , June 2016, ISSN  0949-328X , p. 177–182 , doi : 10.1016 / j.orthtr.2016.02.001 .
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  11. ↑ Anna Hallén, Jan Ekstrand: Return to play following muscle injuries in professional footballers . In: Journal of Sports Sciences . tape 32 , no. 13 , 2014, ISSN  1466-447X , p. 1229-1236 , doi : 10.1080 / 02640414.2014.905695 , PMID 24784885 .
  12. ↑ Pura Muñoz-Cánoves, Jaime J. Carvajal, Adolfo Lopez de Munain, Ander Izeta: Editorial: Role of Stem Cells in Skeletal Muscle Development, Regeneration, Repair, Aging, and Disease . In: Frontiers in Aging Neuroscience . 2016, p. 95 , doi : 10.3389 / fnagi.2016.00095 .
  13. ^ Arnd Krüger : Pep Guardiola. In: competitive sport. 46, 4, 2016, pp. 27-28.
  14. ↑ DM Botha, Y. Coopoo, MK Botha et al .: The effect of hyperbaric oxygen and blood platelet injection therapy on the healing of hamstring injuries in rugby players: a case series report. In: African Journal for Physical, Health Education, Recreation and Dance. Supplement 1, November 2015, pp. 29-39.
  15. ↑ Martin Enserink: Selling the Stem Cell Dream . In: Science . tape 313 , no. 5784 , 2006, p. 160-163 , doi : 10.1126 / science.313.5784.160 .
  16. ↑ Bruce H. Dobkin, Armin Curt, James Guest: Cellular Transplants in China: Observational Study from the Largest Human Experiment in Chronic Spinal Cord Injury . In: Neurorehabilitation and neural repair . tape 20 , no. 1 , 2006, ISSN  1545-9683 , p. 5–13 , doi : 10.1177 / 1545968305284675 , PMC 4169140 (free full text).
  17. ↑ Ninette Amariglio, Abraham Hirshberg, Bernd W. Scheithauer, Yoram Cohen, Ron Loewenthal, Luba Trakhtenbrot, Nurit Paz, Maya Koren-Michowitz, Dalia Waldman, Leonor Leider-Trejo, Amos Toren, Shlomi Constantini, Gideon Rechavi: Donor-Derived Brain Tumor Following Neural Stem Cell Transplantation in an Ataxia Telangiectasia Patient . In: PLoS Medicine . tape 6 , no. 2 , 2009, p. e1000029 , doi : 10.1371 / journal.pmed.1000029 .
  18. ↑ International Society for Stem Cell Therapy - Patient Handbook for Stem Cell Therapy (PDF; 304 kB).