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An update for cord blood clinical trials

I’ve wrote this mini-review for Canadian family cord blood bank “Insception [1]” two months ago. This is online version of review. Please note, that this material is copyrighted by Insception and my CC license doesn’t apply.

Since the introduction to clinical practice in 1988 [2], cord blood (CB) transplantation has gone all the way from experimental procedure to standard of healthcare. Remarkably, CB transplantation made a huge leap from the application initially restricted in pediatrics into the adult clinic. According to EuroCord report [3] (ESTM Cord Blood Banking conference at Pescara, Italy, 2009), the number of unrelated CB transplants is now greater in adults than in children since 2006. It was mostly achieved by implementing of double unit cord blood transplant, currently being almost half the total number of CB transplants in adults in Europe.

Double unit CB transplantation is a relatively new technique, which overcomes the cell dose limitation problem of single CB unit, and is currently moving from clinical trials to widespread clinical use. Another promising way to overcome low cell dose in adult clinic is increasing CB stem cell engraftment in bone marrow. Changing the route of transplantation from intravenous to intra-bone (intra bone marrow) could be the first easiest way to increase stem cell engraftment. Intra-bone CB transplantation is currently undergoing Phases II-III clinical trials in a number of centers. But more intriguing would be a comparison of two techniques – double unit versus intra-bone CB transplant. This study is currently under way in Europe [4] and supervised by EuroCord and EBMT. The preliminary report indicates [4] that intra-bone CB transplant could have some advantages compared to double unit CB, such as: improved disease-free survival, faster platelet recovery and decreased acute graft-versus-host disease incidents. Furthermore, intra-bone transplant of single CB unit could potentially decrease a total cost of cord blood transplantation.

Another interesting approach to increase CB unit engraftment and overall performance in adults is manipulation of stem cell migration and homing in bone marrow. Fate Therapeutics [5] has initiated a Phase I trial [6] for therapeutic agent (PGE2) supporting CB hematopoietic stem cell engraftment. Another therapeutic agent – Sitagliptin, potentially speeding up CB stem cell engraftment (recovery of different types of blood cell counts after transplant) is currently undergoing clinical trial in Indiana University School of Medicine [7]. Co-transplantation of mesenchymal progenitor cells is one more strategy for CB hematopoietic stem cells engraftment facilitation which is now in early phases of clinical trials [8].

Because of the problem of low total cell number per unit of CB, there is a huge interest in developing of hematopoietic stem and progenitor cell expansion techniques. Clinical trials on phases I-III assessing efficacy of CB cell expansion in hematology currently going on all around the word. I’d like to point out two interesting trials in US academic centers and hospitals – Fred Hutchinson Cancer Center [9] (WA, USA) and in MD Anderson Cancer Center [10] (TX, USA). So far, both trials confirmed clinically significant expansion of CB progenitor cells, safety, feasibility of the procedure and now moving to the next phase, assessing efficacy. Israeli company Gamida Cell [11] is running the Phase III of StemEx study [12], assessing the benefit of expanded ex vivo CB units in leukemia and lymphoma patients. Another Gamida’s CB expansion trial – NiCord [13] has started at Duke University.

Because of relatively easy access, absence of ethical controversies coupled with unique combination of immune, progenitor and stem cells, cord blood started to be explored in regenerative medicine. Now we’re witnessing a very interesting period when CB cell transplantation is entering a clinical trials era for treatment of some chronic and degenerative diseases.

A few years ago, Duke University pioneered [14] the application of autologous CB transplantation [15] in children with cerebral palsy (CP). Joanne Kurtzberg recently reported [16](at World Cord Blood Congress, Marseille, France, 2010) preliminary results of 140 children treated at Duke with a good outcome. Now Duke study has expanded to neonatal hypoxic-ischemic encephalopathy [17] and acquired brain injuries. Georgia Health Sciences University has started a similar trial [18], assessing a benefit of autologous CB transplantation in CP. The University of Texas Health Science Center has initiated the clinical trial to determine whether autologous CB transplantation will affect traumatic brain injury in pediatrics [19]. The most intriguing, in my opinion, was a trial announced by Sung Kwang Medical Foundation [20] (South Korea), which for the first time aimed to determine effectiveness of allogeneic (unrelated) CB transplantation in children with CP.

There are more and more trials that have started around the world for CB transplantation in patients with diabetes. In US University of Florida currently conducting a clinical trial [21] to determine whether autologous cord blood transplantation can impact juvenile diabetes (type I). Very similar trial has started in Germany (Technische Universität München [22]). Interestingly, in China there are at least two independent clinical studies (at Qingdao University [22] and Cellonis Biotechnology [23]) assessing safety and feasibility of mesencymal stem cells, derived from CB, in patients with diabetes type I.

The very recent trend in CB transplantation for purposes of regenerative medicine is using allogeneic (related or not related) graft rather than autologous. Well, in the future, the vast majority of customers of regenerative medicine will be “aging boomers”, who didn’t save CB at birth. Now we have got the first data [24], coming from an observational study, that mismatched allogeneic CB cell therapy can be done safely in different non-hematological conditions, which did not required immunosupressive conditioning. The authors of this recently published report [25] evaluated safety of allogeneic mismatched umbilical CB mononuclear cell therapy in 114 patients mostly with neurodegenerative diseases, which was performed in Nanshan Affiliated Hospital of Guangdong Medical College (China). I hope to see the confirmation of these findings in other independent trials. Lastly, I’d like to point out a very interesting clinical trial in Hong Kong (sponsored by China Spinal Cord Injury Network) assessing allogeneic HLA-matched CB cell transplantation in patients with spinal cord injury [26].

If allogeneic CB cell transplantation is really going to work in regenerative medicine, it will be the next “big thing” and “business paradise” for the CB banks. We will get the answer soon. Finally, I’d like to point out that vast majority of “regenerative medicine clinical trials” still on early phases (I-II) and we don’t know yet their therapeutic value.

Disclaimer: Dr. Bersenev is independent research analyst, not associated with any private or public cord blood banks and have no conflict of interest.

PS: Since February 2011, more exciting cord blood trials popped up. You can follow all current updates here [27].