Global trends in clinical trials involving pluripotent stem cells: a systematic multi-database analysis

Abstract

Pluripotent stem cells (PSCs) hold great potential for novel therapeutic approaches to regenerate or replace functionally impaired tissues. Since the introduction of the induced pluripotent stem cell technology in 2006, the number of scientific publications on this topic has constantly been increasing. However, so far no therapy based on PSCs has found its way into routine clinical use. In this study, we examined research trends related to clinical trials involving PSCs based on data obtained from ClinicalTrials.gov, the ICTRP database from the World Health Organization, as well as from a search of all individual databases that are included in the ICTRP using a multistep search algorithm. Following a stringent inclusion/exclusion procedure 131 studies remained that could be classified as clinical trials involving PSCs. The magnitude of these studies (77.1%) was observational, which implies that no cells were transplanted into patients, and only a minority of studies (22.9%) were of an interventional study type. The number of clinical trials involving induced pluripotent stem cells (iPSCs, 74.8%) was substantially higher than the one involving embryonic stem cells (ESCs, 25.2%). However, the picture changes completely when focusing on interventional studies, where in the majority (73.3%) of cases ESCs were used. Interestingly, also the study duration was significantly shorter for interventional versus observational trials (p = 0.002). When focusing on the geographical study regions, it became obvious that the greatest part of all observational trials was performed in the USA (41.6%) and in France (16.8%), while the magnitude of interventional studies was performed in Asian countries (China 36.7%, Japan 13.3%, South Korea 10.0%) and in the field of ophthalmology. In summary, these results indicate that only a limited number of trials were focusing on the actual transplantation of PSCs into patients in a rather narrow field of diagnoses. The future will tell us, if the iPSC technology will ultimately overcome the current challenges and will finally make its way into routine clinical use.

Keywords: Embryonic stem cells; Induced pluripotent stem cells.

Fig. 1. Geographic distribution of studies involving human pluripotent stem cells.

a Global distribution of all clinical trials involving human pluripotent stem cells. b Distribution of all clinical trials involving human pluripotent stem cells. c Global distribution of interventional clinical trials involving pluripotent stem cells. d Distribution of observational clinical trials involving pluripotent stem cells. e Global distribution of all study participants. f Global distribution of interventional clinical trials involving pluripotent stem cells. g Global distribution of observational clinical trials involving pluripotent stem cells. h Comparison between interventional and observational clinical trials and study participants. The horizontal axes have logarithmic scales of different sizes.

Fig. 2. Disease categories targeted in clinical trials involving human pluripotent stem cells.

The legend shown on the top right of Fig. 2 is color coordinated with all three pie charts. a Sub-classification of the category “non-communicable diseases”. b Distribution of clinical trials involving pluripotent stem cells dependent on the targeted disease. c Distribution of observational clinical trials dependent on the targeted disease. d Distribution of interventional clinical trials dependent on the targeted disease.

Fig. 3. Comparison of starting point and study duration dependent on the use of either one of the two stem cell types, hiPSC and hESC.

The blue bars show the starting point and study duration of clinical studies involving hESCs, the orange bars depict the same information for studies involving hiPSC. The green dashed line shows the time of data collection. The x axis shows the time in years, the y axis shows the study numbers. A list of the respective studies can be found in Supplementary Table 1.

Fig. 4. Comparison of starting point and (scheduled) study duration dependent on the study design.

The blue bars show the starting point and study duration of observational clinical studies, the orange bars depict the same information for interventional clinical trials. The green dashed line shows the time of data collection. The x axis shows the time in years, the y axis shows the study numbers. A list of the respective studies can be found in Supplementary Table 1.

Fig. 5. Usage of pluripotent stem cell types (hESC and iPSC) dependent on geographic distribution and study design.

a Distribution of all clinical trials and interventional and observational trials respectively, dependent on the usage of hESC or hiPSC. b Choropleth map presenting the geographic distribution of all clinical trials involving hESCs. c Choropleth map presenting the geographic distribution of all clinical trials involving hiPSCs.