Stem cell cures for everything, Made in Germany by TICEBA

The Heidelberg-based company TICEBA (abbreviated from Tissue & Cell Banking) is not your ordinary run-of-the-mill cell bank. This German company, scientifically advised by the Harvard professor Markus Frank, claims that our skin contains pluripotent stem cells, which are capable of curing all kinds of diseases. This concept is utterly unsupported by scientific literature, and is widely rejected by stem cell scientists. Nevertheless, there is internet evidence that the company’s founder, Christoph Ganss is already treating patients with these cells, in East Asia and even in EU and in Germany. According to certain (sometimes already removed) internet information, patients are being offered autologous “stem cell” injections not only for beauty treatments, but also as cures for type II diabetes, cardiovascular problems, hereditary degenerative eye diseases, and possibly even cancer.

A small price to pay for youth and health

My investigation started with an advertisement in a Lufthansa in-flight magazine, which I was browsing during my return flight from a family visit in Riga in August 2015. The Heidelberg-based company TICEBA advertised to inclined customers on page 41 under the headline “You will age. Your cells won’t” some very exciting service:

“We like a tiny sample of your skin. Separate the stem cells. Store your stem cells in liquid nitrogen. Forever. Then, one day, when old age or illness overtakes you, we re-programme them. Introduce them back into your body. Regenerate you using your younger, stronger, healthier self. It’s not science fiction. Just science”.

As a former stem cell researcher I could not believe this outrageous promise. As soon as I arrived home, I went online to read the TICEBA website. Then, the excitement subsided: nothing of the ad’s promises, only a modest offer of an extraction of a small sample of skin cells and their storage in TICEBA’s own Heidelberg facility, in the immediate vicinity of the University Hospital and the German Cancer Research Center (DKFZ). Little information on what exactly these stem cells might be, and how TICEBA intends to actually apply them. Therefore, I registered as an interested TICEBA customer and was swiftly rewarded via email by a whole bunch of brochures, thanks to the client support assistant Valentina Steinhauser. Then, it became really entertaining.

The scientific philosophy of TICEBA is disarmingly simple: inside our skin, unbeknownst to the world of science, are hidden certain stem cells, highly similar to early pluripotent embryonic stem cells. As my own scientific explainer: under the concept of stem cell pluripotency scientists mean that such cells can differentiate into any cell type of the body and its three embryonic germ layers (endoderm, mesoderm and ectoderm). This is precisely what TICEBA claims to be true of their mysterious skin cells. Another explainer, confirmed by TICEBA: their “technology” has nothing to do with the well-known reprogramming to induced pluripotency (iPS).

The company also referred to these skin cells as “mesenchymal stem cells”, which can be recognized by a particular protein called ABCB5, which they allegedly express on their surface. The procedure goes like this: a TICEBA customer is placed under local anaesthesia, a small piece of skin behind the ear removed, cells are then somehow sorted for ABCB5 marker expression, expanded and stored in liquid nitrogen. An absolute bargain, for only a meagre investment of €4500, plus some petty €450 for the annual storage fee. There is also a 10% family discount on offer, since only heartless monsters would buy the package only for themselves and refuse their loved ones rejuvenated, prolonged and disease-free life, courtesy of TICEBA.

Scientific evidence not needed

Nice as it is, the most puzzling aspect of this Heidelberg cure is that nothing of the kind is known to science. Serious research literature is devoid of pluripotent stem cells in the skin, also the stem cell scientists I spoke to were, to put it mildly, very sceptical. Paul Knoepfler, cell biology professor at the UC Davis School of Medicine and well-known blogger on the subject of stem cell research, explained:

“Unfortunately, outfits like TICEBA are becoming increasingly common all over the world including here in the US. A key question is whether stem cell clinic services and products constitute medical procedures and biological drugs that would require regulatory pre-approval.

In the case of TICEBA specifically, it seems like what their ad is selling is a claim of longer, more youthful life via stem cells. I’m not aware of any current stem cell product that has proven anti-aging properties”.

Thus, I asked Mrs. Steinhauser, not as a fake customer, but as science journalist, for literature references that would support the enticing TICEBA claims on the pluripotency of the skin-residing ABCB5 cells. Steinhauser referred me rather generally to explore the website “PubMed.com”, and mentioned that mesenchymal stem cells have since long proved themselves in clinical studies, as presented on the NIH-powered page ClinicalTrials.gov. However, the outcome of the studies listed there is completely unclear, in fact most are unpublished and thus beyond any scrutiny.

I then approached the German Stem Cell Network, GSCN. The network coordinator Daniel Besser issued this official statement on behalf of the GSCN researchers:

„According to the current stand of research, no pluripotent cells can be naturally derived from the skin. Mesenchymal stem cells, including those from the dermis of the skin, are characterised by their differentiation into the cell types of the mesoderm (e.g., cartilage cells, bone cells, adipose tissue cells or fibroblasts). They cannot by themselves develop into cells of other germ layers. Cells which can do this are known to us only as embryonic stem cells from early embryos and, after extensive reprogramming of somatic cells, as induced pluripotent stem cells (iPS cells)”.

A research-shy physician and a Harvard professor

TICEBA is led by the physician and surgeon Christoph Ganss, born in 1964. According to TICEBA’s own information, Ganss founded the company in 2003 and is “committed to ethical principles”. He received his medical degree from the University of Heidelberg in 1994. It is unclear how much research experience Ganss has had, a PubMed search brought to light only one single paper featuring his name, hidden in a long list of co-authors. This research paper appeared recently in the journal Cell Reports (Schatton et al, 2015). It describes the discovery of immune-regulatory ABCB5-expressing cells in the mammalian skin, thus also indirectly conferring new unique properties to the mysterious TICEBA stem cells. Senior author of this paper is Markus Frank, professor of paediatrics and dermatology at the Brigham and Women’s Hospital, Harvard Medical School (same elite research clinic where until recently the misconduct-tainted scientists Charles Vacanti and Piero Anversa were employed). But Frank is also the only member of the scientific advisory board of TICEBA, as well as the company’s shareholder. The method of isolation and quality assessment of ABCB5 cells from the skin is licensed to Frank and granted by him exclusively to TICEBA and its subsidiary RHEACELL, which specialises in clinical applications. Frank is originally from Germany, also he studied at the medical faculty of the University of Heidelberg, around the same time as his fellow student and now business partner Ganss.

Frank’s research specialty are the ABCB5-expressing cells, which he keeps discovering again and again, in all sorts of tissues and biological functions. ABCB5 belongs to the family of membrane-bound P-glycoproteins, its function is unclear. As mentioned above, Frank and his wife Natasha published recently together with Ganss that ABCB5 is responsible for immune-regulation. Prior to this, ABCB5 proved to play key roles in cell fusion, stem cell function and even placental development. ABCB5-positive cells were found by Frank found above all in tumours, blood, intestines, and, of course, in skin.

Thus, if Frank’s own research on cancerous role of ABCB5 should indeed be correct, it would be somewhat irresponsible to expand ABCB5-expressing skin cells and bring them into a patient. But the fear may be quite unfounded, because although Frank’s research is most valued at top journals such as Nature, some sceptical colleagues rather hold back with their praise.

Nature paper slammed

TICEBA website proudly displays the last year’s Nature publication of its scientific advisor Frank (Ksander et al, 2014). The authors report a novel and clinically highly relevant role of their special cell surface marker. ABCB5 is shown as indispensable for the function of stem cells in the cornea of the eye. Specially purified ABCB5-positive cells from the so-called limbal region of the eye were able to restore the damaged cornea in mice. Thus, I contacted an internationally recognized clinical expert on epithelial stem cells for his advice in assessing the true scientific impact of this Nature paper. Michele De Luca is biochemistry professor and director of the Centre for Regenerative Medicine “Stefano Ferrari” at the Italian Università degli Studi di Modena e Reggio Emilia. He is also, among other achievements, the leading specialist for in vitro cultivation of limbal stem cells and their therapeutic transplantation to restore vision in burn victims. De Luca’s opinion on the value of Frank’s publication could not be harsher:

“Ksander and colleagues suggest that ‘ABCB5 is a limbal stem cell gene required for corneal development and repair’. But genetic data contained in the very same paper clearly argue against a role of ABCB5 both in the development and repair of the cornea, hence in limbal stem cell function. Although ABCB5 knockout mice had some (minor) corneal abnormalities, probably related to regulation of apoptosis, ABCB5 knockout littermates were indistinguishable from wild-type mice through adulthood and their eyes contained all anterior and posterior segment components (how can it then be stated that ABCB5 is thus required for corneal development?). Notably, the ocular surface of ABCB5 knockout mice was covered by a normal, functional corneal epithelium (which evidently developed properly) and wound closure rates of central cornea injuries were not different in ABCB5 knockout and wild-type mice (how can it then be stated that ABCB5 is thus required for corneal repair?). Restoring the corneal epithelium after severe wounding is in fact a hallmark function of limbal stem cells. This notion is in contrast with what have been shown with other proteins truly essential for tissue development and repair”.

De Luca believes that “the corneal abnormalities arising from ABCB5 deficiency could be ascribed to the pro-apoptotic role of ABCB5”, unrelated to stem cells. He and his University of Modena colleague Graziella Pellegrini expressed their (very restrained) criticism in a commentary article in Cell Stem Cell.

No scientific evidence at all

Thus, it looks like Frank’s own data may not necessarily support his scientific claims about the alleged limbal stem cell function of ABCB5. How this paper ended up published in Nature, is somewhat of a mystery to De Luca.

Noteworthy, Frank never goes so far as to insinuate that ABCB5 cells in the skin or any other tissue were anywhere in the vicinity of pluripotency. If not from the scientific advisor, where then did TICEBA get this bizarre idea from? Obviously not from the scientific literature either. Some top-secret company-own research, perhaps? Upon my inquiry, Steinhauser provided me with some “remaining scientific data”.  The document, labelled as “confidential information”, describes TICEBA’s internal studies in which the ABCB5-purified cells from human skin were tested in immuno-suppressed mice for their possible toxicity. Indeed, they proved safe. What TICEBA however cannot demonstrate there, are any experimental results on the alleged pluripotency of the ABCB5 skin cells. Importnantly, according to that document, ABCB5 cells of TICEBA customers are well tested for biocompatibility and surgical applications in human patients.

And found some rather strong evidence on the internet that this is already happening.

Anti-ageing, by TICEBA

With some help of a former Laborjournal colleague, I could name certain enterprises directly offering TICEBA’s cell therapies. First of all, it looks like TICEBA uses patients’ own skin cells for beauty operations for the purposes of “anti-ageing”. According to an endorsement by a beautician Katja Bock on the social network “Medical Tourism City“, the Swiss Seegartenklinik (or Lake Garden Medical Center) in Zurich is highly active in this regard. Indeed, TICEBA and Ganss are listed in the external phone directory of the Seegartenklinik under the reference “stem cells”.

In Austria, the Viennese “absolut schön” private clinic of Doris Wallentin offers in collaboration with TICEBA skin rejuvenation through injection of patient’s cells as “Méthode Cellesthic” (this brand name is owned by Ganss since 2008). Incidentally, there is no mention of the usual pluripotent mesenchymal ABCB5 stem cell drivel. Even Wallentin seems to understand what the TICEBA product really is: simple skin fibroblasts. Another European example: the “Life Bank” in the EU-country Cyprus specializes in storage of tissues such as umbilical cord blood and cooperates closely with TICEBA and Ganss. In a promotional YouTube video of the company, one first sees Dr.  Ganss in a meeting with colleagues. They then load a syringe with something that could be the magical stem cells, then move towards the operation-ready patient. Also, in 2008 Ganss even offered his anti-ageing stem cell services via the German tabloid Bild, price tag: €6000.

Ganss seems to be highly active in East Asia, and also there, he helps wealthy women think they look younger. He is listed as Regenerative Medicine consultant at the Vital Life Wellness Centre at Bumrungrad International Hospital in Bangkok, Thailand. Ganss is praised there as:

“Expert on stem cell research, working closely with Dr. Marcus [Frank -LS] from Harvard University developing ground-breaking technologies that offer customers an exclusive opportunity to use their personal stem cells for regenerative and anti-aging purposes”.

A self-proclaimed “anti-aging researcher” Raymond Probyn narrated in October 2013 on LinkedIn (access now blocked) as follows:

“Dr. Ganss visits the center every 3 months to provide a stem cell consultancy which includes collecting approximately 1cm.sq. biopsies, under local anesthetic, from a cosmetically unobtrusive area, for example from behind the ear, which are transferred to Germany for stem cell extraction , purification and multiplication[…]. The cells are transferred back to the Vital Life clinic where they are infused into the patient via IV over 9 months at 3 monthly intervals. […]Treatment cost: 1.8 million THB (US$ 60,000 ). In date 25 patients have enrolled into the program which was introduced in 2010”.

Curing everything, with magic cells

Elsewhere in East Asia, as the newspaper “Philippine Daily Inquirer” reported in July 2013, a woman suffering from hereditary retinal degenerative disease retinitis pigmentosa was partially cured, thanks to TICEBA. The company apparently operates in the Philippine capital Manila a head office, which is personally manned by Ganss. According to the report, patient’s skin cells have been isolated locally and brought frozen to Heidelberg, where they were expanded. Back in the Philippines, one syringe with 50 microliters of cells was injected into the eye of the patient, the rest intravenously into her body, for the purpose of “overall wellness and rejuvenation”. When asked for his opinion about this, the Italian eye specialist De Luca was at a loss simply trying to comprehend the medical rationale of this therapy. The Inquirer article also described where the TICEBA-mediated treatment of retinitis pigmentosa can be sought: from the ophthalmologist Harvey Uy at St. Luke’s Medical Center in Manila. This was also confirmed by this clinic’s own press release (now deleted, but available to me as a saved copy, like the other removed websites).

Another Philippine treatment offer, which rapidly disappeared from the internet during my investigation, was that of TICEBA mediated stem cell treatment of cancer at the Royal Preventive Medical Clinic in Makati. There, it was about the so-called tumour-vaccination: dendritic cells, equipped with cancer-specific antigens, to home in on the tumour cells inside the patient. The description goes:

“Customized Dendritic Cell Therapy for Tumor Stem Cells is offered by our partner TICEBA, a highly innovative German life science company. Dendritic Cell Therapy aims to treat the tumor initiating cells which remain after chemotherapy,along with the surrounding potentially cancerous cells. This treatment can induce immunity against cancer and completely degenerate an existing tumor.

Ongoing clinical studies use tumor antigen bearing Dendritic Cells as vaccines to prevent breast, lung, prostate, and renal cell cancers. This treatment aims to alleviate tumor initiating cells which have been identified in solid cancers. These cells are capable of self renewal and differentiation, which are responsible for tumor growth and metastasis. Targeting tumor initiating cells can eradicate cancers that have developed resistance against systematic therapy.

TICEBA, though the Royal Preventive Clinic, offers this healing therapy with a patented stem cell marker in an attempt to prime patient owned, isolated, and maturated dendritic cells for tumor therapy”.

In fact, even TICEBA itself proudly reports about this research, done in collaboration with the University Hospital Mannheim (which is located close to Heidelberg). The cancer antigen is, unsurprisingly, ABCB5. If one recalls the recent Frank publication (with Ganss as co-author), it is rather evident that these ABCB5-bearing dendritic cells are likely nothing but the usual magical cells from the skin.

Ganss and his company also allegedly healed the geriatric Filipino business tycoon Jose S. Concepcion Jr from age-related diabetes. At least, that is what one learns from another report in the Philippine Inquirer, from February 2013. Also Conception’s wife was treated by Ganss for hypertension with the same method, but according to her own statement, it did not help her. Her husband’s diabetes was not cured either, and even he himself suspects his improved well-being to be a placebo effect. Conception is quoted: “I feel stronger, and maybe it’s psychological. But Dr. Ganss has a databank of people who have had it. I don’t think people would be doing it if it didn’t work”.

Get well in Germany

The article also mentions the quasi-magical recovery of a relative of Conception, who was suffering from serious cardiovascular problems until she was cured by TICEBA. According to information in the Lifestyle Asia magazine, the named patient was transferred to TICEBA by the surgeon Rex Gloria, who also works for the aforementioned Royal Preventive Clinic. The article narrates: the patient “commuted to Germany for stem cell infusions directly into her heart”. Thanks to Ganss and TICEBA, she was reportedly cured and recommended the method to her entire relationship.

A possible treatment in Germany opens a new understanding of the TICEBA business model. Many dubious companies offer even more dubious stem cell therapies throughout the world. However, German medical care is held in highest esteem among patients worldwide. Desperate and often terminally ill people from Eastern Europe and Asia spend their last dime and borrow money which they cannot afford, only to be treated in Germany. Many blindly trust Germans doctors, and expect them to succeed where the doctors in their own home countries seemingly failed (in fact, it wouldn’t be surprising if a private visit in a German clinic alone might have a major placebo effect in itself). And it seems, Herr Dr.  Ganss enjoys a lot of patient trust in East Asia.

There is more internet evidence that Ganss might be treating patients with his stem cell method in Germany, possibly with help of other German doctors. A Chinese-language website, when automatically translated, suggests that Ganss has been invited to speak in China by a local promoter of medical tourism. According to the website, Ganss and his host promised their audience cures for diabetes using ABCB5 stem cells from TICEBA. For such diabetes therapy, patients were invited to take three separate trips to Germany: first for cell removal, then for the cell injections into the bloodstream and finally into the pancreas.

The Beijing-based medical tourism provider L’Avion reported on its Chinese-language webpage about TICEBAs ABCB5 stem cell treatment of diabetes and presented Ganss as a “TICEBA expert team” leader. The other team members were the German diabetologists Christoph Hasslacher and Frank Heckmann, both officially associated with the private ATOS clinic in Heidelberg. When I asked these two doctors about their “TICEBA expert team” membership and the above-mentioned treatment of Filipino patient Conception, Hasslacher denied, also on behalf of Heckmann, to have ever been involved therein. Yet when I specifically inquired whether he and Heckmann ever treated any diabetes patients with the TICEBA cells: there Hasslacher remained silent. But the Chinese L’Avion website soon disappeared from the internet.

Surgery without permit

On its website, TICEBA proudly displays its official permit for tissue extraction and storage. The company is based in Heidelberg, a German town in the federal state of Baden-Württemberg, thus the permit issuing state authorities are the Regierungspräsidum located in Tübingen and in Karlsruhe. The press relations officer of the Regierungspräsidium Tübingen, Daniela Hüttig, explained: “a special permit for marketing authorization (administration to patients as well as clinical testing) is required within the EU (…). The company has been informed about this orally and in writing”. Thus, if the above reports are true, TICEBA would be acting without an official permit and against state laws by treating patients in Germany and EU with cells produced in Heidelberg.

The Karlsruhe branch of the Regierungspräsidium made it even clearer. TICEBA does not have the necessary permits to market or distribute the tissues in Germany or EU, but it also lacks such permit for their export outside the EU, according to the press relations officer Joachim Fischer. In fact, TICEBA did not even apply for those yet, as Fischer confirmed in August 2015.

Patients’ lives vs money

Thus, it is quite possible that TICEBA might be treating patients with their autologous skin cells, in Asia, Europe and perhaps even in Germany, without any proper scientific justification or an official permit. This is potentially dangerous for the patients, to the very least given the very real risk of infection or other errors during invasive surgery in this apparently pointless therapy. Another danger is: patients believing themselves cured would neglect taking their vital life-saving medicine like insulin or chemotherapy. The TICEBA miracle cure could therefore quickly turn fatal. Do those who make money of them take these concerns seriously?

I have tried several times to obtain any statement at all from the TICEBA leadership. The CEO Ganss and the chief scientist Frank let all my email inquiries go unanswered. At some point, I was invited by the TICEBA office manager Eva-Maria Schork to visit the company in Heidelberg. When I gladly accepted the invitation, but expressed my wish to meet Ganss in person, the invitation was silently withdrawn.

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