35 Years of Cell and Gene Therapy Research: Where the Science Moved and Where It Stalled

Cell and gene therapies have been in active development since the late 1980s. Some have become routine clinical practice. Others have shown early promise, attracted substantial research investment, and then stalled in the transition from laboratory to patient. Understanding why some therapies succeeded and others did not - and how research activity and geographic contributions shaped those outcomes - requires looking at the field as a whole rather than focusing on individual breakthroughs.

A team of researchers at Kyoto University, working in collaboration with Arthur D. Little Japan, took exactly that approach. Using the PubMed and OpenAlex databases, they accessed over 160,000 papers related to cell and gene therapy published between 1989 and 2023, and conducted a comprehensive bibliometric analysis of how the field developed across three and a half decades.

What Kept Growing and What Stalled

Two branches of the field showed continuous growth throughout the study period. Research on hematopoietic stem cell transplantation - including bone marrow transplantation - increased steadily in volume and maintained momentum into clinical practice. Ex vivo gene therapy, which involves modifying a patient's cells outside the body before reinfusing them, followed a similar trajectory of sustained growth.

Two other major areas showed a different pattern. Mesenchymal stem cell therapy, which uses cells that respond to inflammation and injury, saw significant early research activity but has stagnated in its transition from laboratory settings to clinical use. Despite thousands of published studies, the number of approved mesenchymal stem cell therapies remains small and their clinical benefit in many applications has not been consistently established. In vivo gene therapy - delivering genetic material directly into a patient's body rather than to modified cells - showed a similar pattern of research activity not translating cleanly into widespread clinical application.

The distinction between these trajectories reflects a recurring challenge in the field: generating positive results in cell and animal models does not reliably predict success in human trials, and the regulatory and manufacturing requirements for human therapies introduce barriers that bibliometric activity alone cannot overcome.

Geography and Impact: Who Publishes, and Who Influences

The analysis revealed striking geographic patterns in both quantity and quality of research output. The United States and China lead the field in both the number of papers produced and the citation impact of those papers. Japan reliably produces large volumes of cell therapy research but shows a relative deficit in papers that achieve significant qualitative influence on the field.

The most impactful papers - those with the highest citation rates - tended to emerge from international collaborations. Strong collaborative ties exist between Europe and the United States, and within Europe itself. Cross-continental work consistently outperformed single-country research in terms of influence.

"It is clear that international collaborative research tends to lead to high-impact papers, confirming strong ties between Europe and the United States, as well as strong connections within Europe," said team leader Sumimasa Nagai.

The analysis also noted that the current geopolitical landscape - including funding changes and shifts in research priorities across major contributor countries - is likely to affect these patterns going forward. The researchers did not attempt to project future trends, but the observation that high-impact work depends heavily on international collaboration raises questions about what happens to that output when collaboration becomes more difficult.

The Purpose of Looking Backward

The study was designed to serve a practical planning function rather than simply document history. By systematically mapping where research resources have been concentrated, which areas have achieved clinical translation, and which collaborative structures have generated the highest-impact science, the analysis provides a foundation for decisions about where to direct future investment.

For Japan specifically, the researchers aim to use the findings to help direct the country's recognized strengths in regenerative medicine, cell therapy, and gene therapy toward more effective pathways to clinical and social implementation. Japan's contribution to high-impact literature lags its contribution to total publication volume - understanding that gap is a prerequisite for addressing it.

Future work from the team plans to integrate patent data, regulatory information, and funding histories alongside bibliographic data, building a more complete picture of how science moves - or fails to move - from basic research through development to approved clinical use.

The paper, "Advancement in Cell and Gene Therapy Research: a 35-Year Bibliometric Perspective," was published on January 10, 2026 in Cytotherapy (doi: 10.1016/j.jcyt.2026.102056). The research was supported by the Japan Agency for Medical Research and Development under the Acceleration Program for Regenerative Medicine and Cell and Gene Therapy.