Stem Cell Therapy: Facts And Fiction

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This opinion paper is a short overview of the present state of the translation of stem cell therapy from the bench to the clinic. The hype generated by the good medical potential of stem cells has lead to a whole lot of clinics worldwide claiming to have the cure for each conceivable condition. This fraudulent practice is removed from the truth of scientists and bona fide firms. Much effort is put into addressing all the hurdles we have been encountering for the secure use of stem cells in therapy. By now, a big variety of clinical trials are booking very exciting progress, opening a sensible path to the use of these wonderful cells in regenerative medicine.

Keywords: Embryonic stem cells, induced pluripotent stem cells, stem cell therapy, clinical trial, regenerative medicine, security

When you open your web browser and type ‘stem cell therapy’ into your search engine, you're going to get over 18 million results within the blink of an eye fixed. Strikingly, the overwhelming majority of the highest hits, together with the commercials on the side of your page, are from corporations and hospitals offering stem cell therapy to deal with nearly any condition. Take for example the clinic of Prof. Smikodub (http://cell-treatment.com). They promise a cure for diabetes, anemia and cirrhosis, but in addition, brace your self, for fading potency (yes, sexual issues), sterility, cancer and HIV. And, who is Prof. Smikodub? You'll anticipate an eminency in stem cell research to be leading such a revolutionary healthcare programme. Well, Pubmed yields exactly seven papers for Prof. Smikodub, all of them in russian, two of them on using hematopoietic stem cells to deal with most cancers (an interesting idea if you ask me). The reality is that Mr. Smikodub, and all the others offering the miracle cure to actually any of our issues, are a fraud. Sadly, clinics similar to Mr. Smikodub’s have been popping out of the bottom like mushrooms, and never only in fishy looking locations such as the pink-light district of Moscow. Celltex Therapeutics is predicated in Houston, Texas, and has been topic of much controversy due to questionable practices, and is now being completely grilled (and hopefully closed) by the US Food and Drug Administration (www.biopoliticaltimes.org/article.php?id=6284; www.nature.com/information/stem-cell-therapy-takes-off-in-texas-1.10133). Another instance comes from XCell-Center in Dusseldorf, that exploited a loophole within the German law to cost as much as 25.000 € for experimental procedures. The clinic has now been closed after the death of an 18-month outdated baby after a stem cell infusion in the brain (www.msrc.co.uk/index.cfm/ fuseaction/present/ pageid/1831).

One of many hints that a clinic could also be a scam is that they provide therapies for a big number of situations using one and the identical sort of stem cell, mostly isolated from a part of the body that's totally different to the half being treated. There are lots of different types of stem cells, including embryonic stem cells and grownup stem cells. Whilst embryonic stem cells originate from the earliest stage of development, adult stem cells will be found in most (if not all) of the tissues of the physique. Adult stem cells differ from embryonic stem cells in that they may solely spontaneously generate cells from the identical lineage as they are. For example, hematopoietic stem cells can generate blood, neural stem cells can produce neurons, however neural stem cells will not make blood. It's therefore vital that the kind of stem cells is acceptable for the handled disease. Conversely, embryonic stem cells may very well be theoretically used to obtain cells of all lineages, as they are rather more primitive than adult stem cells, and retain the embryonic ability to form a complete particular person. Finally, there are induced pluripotent stem cells, essentially the most exciting Japanese export for the reason that Tamagochi. These cells were first described by Takahashi and Yamanaka in 2006, and since then have boomed on the earth of stem cell research. They basically are terminally differentiated grownup cells which have been send again to their embryonic state by inducing the overexpression of some genes. These genes are ready to change on the pluripotent capacity of the cell, making it now possible to generate embryonic stem cell-like cells from nearly any cell from any person.

Disappointingly, we are nonetheless dealing with a number of important problems in the translation of any of those cell sorts from the bench to the clinic.

On one hand, we have practical problems associated to the way in which stem cells are cultured, and significantly embryonic and induced pluripotent stem cells. Currently, though much effort is spend into developing clinical grade tradition techniques, many of the embryonic stem cell lines are still grown involved with xenogenic merchandise and cells. Another bottleneck that is more difficult to unravel is that human stem cells can hardly be bulk cultured. To have the ability to successfully treat a affected person, a large number of cells are needed, and with the present tradition strategies that is, to place it mildly, challenging.

The differentiation protocols are one other important level of consideration. For a differentiation protocol to be useful in a clinical setting, it has to be able to efficiently induce the differentiation of the stem cells into a selected cell kind. The protocol ought to yield solely the particular target cell, the differentiation needs to be terminal (i.e. the cells should not be capable to revert to a pluripotent state) and there needs to be no undifferentiated cells left. If a protocol to differentiate to insulin producing beta cells additionally yields muscles, neurons, and a plethora of other cells, it's not appropriate to inject it right into a patient’s pancreas. And, importantly, if there are nonetheless pluripotent cells within the tradition, these cells may have the flexibility of forming tumours in the recipient. It's a unhappy fact that most of the published papers on differentiation protocols exaggerate their results and show very hard to reproduce in other laboratories.

The sources of the embryos used to derive the ESC lines, and the stem cells themselves (of any sort) are nonetheless very poorly characterized. Much work is still to be accomplished to succeed in a consensus on which are the mandatory assessments to ensure that a line is safe to make use of. One of the points which are currently receiving most consideration on this sense is the genomic instability embryonic and induced pluripotent stem cells display. Many of the abnormalities these cells carry are very paying homage to those acquired by most cancers cells. It is therefore essential to judge if these abnormalities lower the capability of mutant stem cells to terminally differentiate and increase the danger of producing (malignant) tumours.

One of the problems of testing the power of stem cells to form tumours is that each one work performed for human stem cells is carried out in mice. Although it is obviously one of the best we are able to do, the mouse is not the pure atmosphere of human cells, and it might properly be that human cells just grow better in a human environment. Therefore, though ends in mice show no tumorigenicity of human cells, they aren't a guaranty for safety.

That poorly characterized stem cells can generate tumours in-vivo in the human has been sadly illustrated by the case of a 13-year outdated patient in Israel. His dad and mom had taken him 3 times to Moscow for a stem cell therapy with foetal neural stem cells in a determined try and cure him from ataxia telangiectasia. The outcome was that the boy developed tumours on his spinal cord. The surgeons who eliminated the tumours proved that the cells didn't belong to the patient, but to at the very least two genetically completely different people, one of them female (Amariglio et al., 2009; Nature Reports Stem Cells, 2009, www.nature. com/stemcells/).

The ultimate problem, and doubtless the one most contributing to a false feeling of hope amongst terminally in poor health patients, is that the literature, and consequently the press, is plagued with reviews that seem nice at first sight, https://therapywhitstemcells.com/ however by which there are not any appropriate control groups or have very brief-term or exaggerated outcomes.

As an illustration, in 2008 Geffner and collaborators printed that the administration of autologous bone marrow stem cells into spinal cord damage patients improves their quality of life. What the authors do not take into account in their work is that it is known that there's a placebo impact in spinal cord surgery trials that they did not rule out, and that through the surgical procedure they carried out different interventions subsequent to the stem cell infusion for which they didn't management within the research (Nature Reports Stem Cells, 2009).

The case of the paper of Bible and collaborators of 2009 is an example of a work with an exaggerated press launch. The press release mentioned they might fill a gap left by stroke harm with new brain tissue within seven days. The paper in actual fact only proved that they may, in rats, fill the opening with a scaffold consisting of little spheres coated with stem cells. The vast majority of the outlet was stuffed with scaffold, and the obtained tissue was unstructured and thin. As well as, it was solely a seven-day experiment and further cell survival was not assessed (Nature Reports Stem Cells, www.nature.com/stemcells/).

The very fact is that there are in the meanwhile very few stem cell therapies with sufficient medical evidence of success to contemplate them as but as acceptable. The most effective outlined and most extensively used one is bone marrow transplantation to treat situations of the blood or the immune system.

However, many potential stem cell remedies are at present being tested in animal fashions and some have already been delivered to clinical trials. Through the past meeting of International Society for Stem Cell Research in Yokohama (www.isscr.org), several researchers and corporations introduced their ongoing or just lately accomplished section I and phase II clinical trials for stem cell therapy. The point all these trials had in common was that the principle end point of the research was safety, which is a key concern that each one these ‘wonder stem cell clinics’ unashamedly ignore.

For instance, Ann Tsukamoto of Stem Cells Inc (www.stemcellsinc.com) presented their work using human neural stem cells. These cells are now being clinically assayed to treat two sorts of neurodegenerative disorders and spinal cord damage. The corporate additionally works on the development of a remedy for retinal disorders such as age-related macular degeneration and Alzheimer’s illness. The results from their first trials are encouraging, as no tumour formation or issues related to the transplants have been noticed.

Katarina Le Blanc from the Karolinska Institutet in Sweden spoke about their results on using mesenchymal stem cells for the therapy of graft-versus-host disease (Ringden and Le Blanc, 2011). Mesenchymal stem cells appear to have an anti-inflammatory effect, and part I and part II research have proven that 50% of the patients reply to treatment with these cells. These studies have been, once more, principally directed to handle security points. In all the handled people, no toxic or inflammatory reactions had been discovered on the quick time period. In an extended-time period examine, the autopsy of 18 of these patients showed that there was no ectopic tissue formation or tumours, although they may discover traces of the DNA from the donor in numerous tissues of the acceptor (von Bahr et al., 2012).

All in all, the preliminary euphoria raised by the advent of embryonic stem cells is calming down. In a sense, we tried to run before learning to walk. Now, scientists and clinicians are cautiously looking into lifelike clinical purposes of stem cells, with the perpetual optimism characteristic of folks that spend their lives considering that the experiment they're doing right now's the last one they should prove their Nobel Prize price discovery. And sometimes, they are right.

The writer needs to thank Karen Sermon and Mieke Geens for the essential studying of the manuscript. Claudia Spits is a postdoctoral fellow at the FWO Vlaanderen, and has no conflict of curiosity.

1. Amariglio N, Hirshberg A, Scheithauer BW, et al. Donor-derived brain tumor following neural stem cell transplantation in an ataxia telangiectasia affected person. PLoS Med. 2009;6:e1000029. doi: 10.1371/journal.pmed.1000029. [DOI] [PMC free article] [PubMed] [Google Scholar]2. Bible E, Chau DY, Alexander MR, et al. The assist of neural stem cells transplanted into stroke-induced brain cavities by PLGA particles. Biomaterials. 2009;30:2985-2994. [Google Scholar]3. Geffner LF, Santacruz P, Izurieta M, et al. Administration of autologous bone marrow stem cells into spinal cord damage patients by way of multiple routes is protected and improves their quality of life: comprehensive case studies. Cell Transplant. 2008;17:1277-1293. doi: 10.3727/096368908787648074. [DOI] [PubMed] [Google Scholar]4. Ringden O, Le Blanc K. Mesenchymal stem cells for therapy of acute and chronic graft-versus-host illness, tissue toxicity and hemorrhages. Best Pract Res Clin Haematol. 2011;24:65-72. doi: 10.1016/j.beha.2011.01.003. [DOI] [PubMed] [Google Scholar]5. Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by outlined factors. Cell. 2006;126:663-676. doi: 10.1016/j.cell.2006.07.024. [DOI] [PubMed] [Google Scholar]6. von Bahr L, Batsis I, Moll G, et al. Analysis of tissues following mesenchymal stromal cell therapy in humans indicates limited long-time period engraftment and no ectopic tissue formation. Stem Cells.