Perinatal derivatives application: Identifying possibilities for clinical use

Gindraux F, Hofmann N, Agudo-Barriuso M, Antica M, Couto PS, Dubus M, Forostyak S, Girandon L, Gramignoli R, Jurga M, Liarte S, Navakauskiene R, Shablii V, Lafarge X, and Nicolás FJ.

Frontiers in bioengineering and biotechnology, 2022. https://doi.org/10.3389/fbioe.2022.977590

PMCID: PMC9595339

Perinatal derivatives are drawing growing interest among the scientific community as an unrestricted source of multipotent stromal cells, stem cells, cellular soluble mediators, and biological matrices. They are useful for the treatment of diseases that currently have limited or no effective therapeutic options by means of developing regenerative approaches. In this paper, to generate a complete view of the state of the art, a comprehensive 10-years compilation of clinical-trial data with the common denominator of PnD usage has been discussed, including commercialized products. In summary, the main aims of this position paper are to show possibilities for clinical application of PnD and propose an approach for clinical trial preparation and registration in a uniform and standardized way.

Most clinical trials concentrate on applying hUC-MSC (n = 200) followed by hAM (n = 60), and just the remaining ones are using other multiples sources (n = 80) (Figure 3). Regarding the product presentation, we found a quite homogeneity, as the majority of clinical trials were conducted using cells (n = 248) and/or tissue (n = 104), while just a few (n = 7) involved TF. It is worth noting that all of the clinical trials were conducted using allogenic PnD. However, it should be pointed out that autologous cells from different origins were sometimes combined to PnD.

Cell-based products were the most frequently used in clinical trials implementing PnD (n = 248 out of 340, 72.6%). A systemic approach was used in 57.5% cases, while local administration were used in 38.1% and in two clinical trials (0.8%) cells were injected locally and systemically in a simultaneous manner. From PnD cell products, MSC were the most frequently used (93.5%). Perinatal MSC in most cases were used systemically (60.6%) and locally in the rest of cases (34.2%). hAEC were used only in 3.6% of clinical trials utilizing PnD. In contrast to MSC, hAEC-based products were administrated locally. Clinical trials implementing hAM also constituted a significant part (22.6%) of clinical trials utilizing PnD. Due to their characteristics, all hAM products are applied locally. 

Graphical abstract of the study. The United States Clinical Trial Registration Portal (clinicaltrials.gov) was searched for 10-year period from 01/01/2011 to 07/10/2020 with different search-terms. From the keyword-based search, a number of clinical trials were identified. After removing studies for curing, the remaining 340 trials were analyzed. The main conclusions are shown and a more detailed registry is proposed.