Allogenic banking of dental pulp stem cells for innovative therapeutics

Medical research in regenerative medicine and cellbased therapy has brought encouraging perspectives for the use of stem cells in clinical trials. Multiple types of stem cells, from progenitors to pluripotent stem cells, have been investigated. Among these, dental pulp stem cells(DPSCs) are mesenchymal multipotent cells coming from the dental pulp, which is the soft tissue within teeth. They represent an interesting adult stem cell source because they are recovered in large amount in dental pulps with non-invasive techniques compared to other adult stem cell sources. DPSCs can be obtained from discarded teeth, especially wisdom teeth extracted for orthodontic reasons. To shift from promising preclinical results to therapeutic applications to human, DPSCs must be prepared in clinical grade lots and transformed into advanced therapy medicinal products(ATMP). As the production of patient-specific stem cells is costly and time-consuming, allogenic biobanking of clinical grade human leukocyte antigen(HLA)-typed DPSC lines provides efficient innovative therapeutic products. DPSC biobanks represent industrial and therapeutic innovations by using discarded biological tissues(dental pulps) as a source of mesenchymal stem cells to produce and store, in good manufacturing practice(GMP) conditions, DPSC therapeutic batches. In this review, we discuss about the challenges to transfer biological samples from a donor to HLA-typed DPSC therapeutic lots, following regulations, GMP guidelines and ethical principles. We also present some clinical applications, for which there is no efficient therapeutics so far, but that DPSCs-based ATMP could potentially treat.

Human pluripotent stem cells:From biology to cell therapy

Human pluripotent stem cells(PSCs),encompassing embryonic stem cells and induced pluripotent stem cells,proliferate extensively and differentiate into virtually any desired cell type.PSCs endow regenerative medicine with an unlimited source of replacement cells suitable for human therapy.Several hurdles must be carefully addressed in PSC research before these theoretical possibilities are translated into clinical applications.These obstacles are:(1) cell proliferation;(2) cell differentiation;(3) genetic integrity;(4) allogenicity;and(5) ethical issues.We discuss these issues and underline the fact that the answers to these questions lie in a better understanding of the biology of PSCs.To contribute to this aim,we have developed a free online expression atlas,Amazonia!,that displays for each human gene a virtual northern blot for PSC samples and adult tissues(http://www.amazonia.transcriptome.eu).

A giant crocodile in the Dubois Collection from the Pleistocene of Kali Gedeh(Java)

The fauna of the Pleistocene Homo-bearing sites of Java has been well known for more than a century.A recent revision of the crocodylian remains confirmed both the validity of Gavialis bengawanicus and the synonymiza-tion of Crocodylus ossifragus with C.siamensis.Here we report on a still unpublished crocodylian specimen collected by Eugene Dubois in the latest Early Pleistocene of Kali Gedeh that can be tentatively referred to the genus Crocodylus.The size of the specimen,the approximately 1 m long lower jaw in particular,indicat-ed that this crocodile attained a total length of approximately 6 or 7 m.Along with specimens from the Plio-Pleistocene of Africa,this material provides evidence for gigantism in Crocodylus.It is not clear whether or not the‘temperature-size rule’applies to fossil crocodylians,but due to the growing interest in predicting future temperature-related size changes of the extant organisms,it would be interesting to study in detail the past reac-tion to temperature changes of crocodylians and other terrestrial ectothermic animals.