Comprehensive narrative review on the analysis of outcomes from cell transplantation clinical trials for discogenic low back pain

Preclinical to clinical translation for intervertebral disc repair: Effects of species‐specific scale, metabolism, and matrix synthesis rates on cell‐based regeneration

“…[81][82][83][84] Despite positive results such as increased disc fluid content in treated patients reported at 1-and 2-year follow-up, there is an overall scarcity in the literature on clinical trials and published reports tend to be vague in their shortcomings and no tremendous breakthroughs have been reported. 5,81,85 It appears that follow-up assessments are typically from 6 months to 3 years, whereas the results of this work predict a longer timeframe for detectable functional regeneration which may contribute to ineffective clinical outcomes and conclusions. Furthermore, many studies only report on pain and disability (Visual Analogue Scale and Oswestry…”

“…It is speculated that this may explain the variable results emerging from trials and the failure of cell-based regeneration to be adopted clinically. 5,76,[105][106][107][108][109] Despite the important insights provided in this work, it is important to bear in mind that cell-based therapies first and foremost initiate matrix deposition and compositional changes to the disc and this is the extent of predictions within this work. This work is not capable of predicting complete restoration of the IVD structure and/or biomechanical function.…”

“…A significant hurdle for potential cell‐based therapies is the subsequent survival and regenerative capacity of implanted cells 22,29,65–67 . While many exciting developments have demonstrated promise in this regard preclinically, cell‐based therapies for IVD degeneration fail to translate equivalent clinical efficacy 5,68–70 . As a result, an urgency to ascertain the clinical relevance of different animal models has not only ethical merit but also important scientific value for accelerated and successful translation.…”

“…In addition to differences in cell density between species, an appreciation needs to be afforded to the number of cells to be injected into the disc in terms of how these cell doses compare to the resident cell population and how this translates from a preclinical animal model to a human. From reviewing clinical trial parameters it has been reported that total cell numbers ranging from 1 to 40 million cells are being used (excluding bone marrow concentrates) 5,76 . Furthermore, it appears that just as much variation exists among preclinical studies, with rat models receiving a range of 2–25 thousand cells and goat typically receiving 1–5.5 million cells 38–41,57,64 .…”

“…This is a systematic framework for performing more humane animal research and is a highly relevant topic across the biomedical field. Furthermore, even after demonstrating safety and efficacy in animals, many cell‐based therapies for IVD degeneration still do not appear to work to the same extent in humans 5 . Therefore, there is a pressing need to ascertain the clinical relevance of different animal models, not only for important scientific and ethical merit but to further accelerate the prospects of more successful clinical translation.…”