A Tribute to Professor Alexander Friedenstein and His Outstanding Achievements in the Area of Stromal Stem Cells

Dear Colleagues,

Professor Alexander Friedenstein is credited as the discoverer of stromal progenitor cells, later called mesenchymal stem cells (MSCs). He defined them as stroma-resident cells that are (1) highly proliferative and clonogenic in vitro and (2) capable of extensive self-renewal and multi-lineage differentiation in vivo, thus fulfilling the main criteria attributed to stem cells. Using several in vivo transplantation models, he and his colleagues were able to demonstrate that single-cell-derived clones of stromal progenitors had an intrinsic ability to form bone, cartilage and connective tissues in vivo. This achievement is hard to underestimate, not only in terms of stem cells in general, but also in terms of cell therapies and tissue engineering developments that followed on from his discovery and continue to grow exponentially to the present day.

Alexander Friedenstein was born on the 24^th of June 1924 in Kyiv. His family relocated to Moscow in 1928, where he graduated with a degree in Medicine in 1946. In 1950, he obtained a PhD in skeletal regeneration in high vertebrates, and in 1960, he was awarded a higher doctorate on the histological origins of extra-skeletal osteogenesis. In the late 1960s and early 1970s, he published a number of seminal articles on stromal precursor cells for osteogenic tissues that were later popularised and disseminated worldwide through his collaboration with Dr Maureen Owen in Oxford. In 1991, Dr Arnold Caplan coined the term MSCs to refer to these stromal progenitors; although this terminology remains a matter of active debate, it continues to provoke a tremendous amount of interest in the scientific community. Cell therapy applications with MSCs or their derivatives (secretomes, extracellular vesicles, etc) continue to expand into medical fields beyond skeletal regeneration. MSC-based bioinks are being used in tissue regeneration and disease modelling. For the bioengineering community, the works of Alexander Friedenstein remain highly influential and open up new avenues for further exploration, for example:

1. How can we best isolate and culture MSCs in order to maximise their desired function(s)?
2. The in vivo tissue identity of MSCs as perivascular cells and the therapeutic implications of this identity; MSC migration.
3. How can we enhance the desired functions of endogenous MSCs?
4. The heterogeneity of cultures of MSCs as they relate to their clinical effects.
5. How can we control MSC differentiation or trophic activity through their microenvironment, including smart biomaterials?
6. How can we effectively isolate MSCs-derived extracellular vesicles and what are the methods that can be used to reinforce their therapeutic signatures?
7. What are the benefits and limitations of MSCs versus MSC-derived extracellular vesicles for therapeutics?

On the occasion of Professor Alexander Friedenstein’s centenary in June 2024, Drs Elena Jones, Dimitrios Kouroupis and Rodrigo Somoza are editing a Special Issue entitled "Tribute to Professor Alexander Friedenstein and His Outstanding Achievements in the Area of Stromal Stem Cells" to celebrate his memory. Contributions can take the form of original research articles or reviews that include, but not limited to, the above aspects of his legacy, as well as any new developments in the area of MSCs and their applications in regenerative medicine.

Dr. Elena A. Jones
Dr. Dimitrios Kouroupis
Dr. Rodrigo Somoza
Guest Editors

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