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

A special issue of Bioengineering (ISSN 2306-5354). This special issue belongs to the section "Regenerative Engineering".

Deadline for manuscript submissions: 31 May 2024 | Viewed by 2950

Special Issue Editors

Leeds Institute of Molecular Medicine, School of Medicine, University of Leeds, Leeds LS2 9JT, UK
Interests: mesenchymal stem cells/multipotential stromal cells (MSCs); bone regeneration; cartilage regeneration; osteoarthritis; regenerative medicine; regenerative orthopedics; MSC senescence
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Department of Orthopaedics, Division of Sports Medicine, Diabetes Research Institute, Cell Transplant Center, University of Miami, Miller School of Medicine, 1450NW 10th Ave, Room 3012, Miami, FL 33136, USA
Interests: mesenchymal stem cells/multipotential stromal cells (MSCs); MSC trophic and immunomodulatory actions; MSC functionalization ex vivo; inflammation and fibrosis reversal; synovitis; osteoarthritis; regenerative sports medicine; regenerative orthopaedics
Special Issues, Collections and Topics in MDPI journals
Department of Biology, Case Western Reserve University, Cleveland, OH, USA
Interests: mesenchymal stem cells/multipotential stromal cells (MSCs); cartilage repair and regeneration; mechanisms of bone invasion during metastasis

Special Issue Information

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 24th 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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Published Papers (2 papers)

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Editorial

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3 pages, 192 KiB  
Editorial
Mesenchymal Stem/Stromal Cell-Derived Small Extracellular Vesicles (MSC-sEVs): A Promising Treatment Modality for Diabetic Foot Ulcer
by Dimitrios Kouroupis, Lee D. Kaplan, Camillo Ricordi and Thomas M. Best
Bioengineering 2023, 10(10), 1140; https://doi.org/10.3390/bioengineering10101140 - 28 Sep 2023
Viewed by 759
Abstract
Diabetic foot ulcer (DFU) is associated with neuropathy and/or peripheral artery disease of the lower limb in diabetic patients, affecting quality of life and leading to repeated hospitalizations and infections [...] Full article

Review

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Review
Mesenchymal Stem/Stromal Cells: Immunomodulatory and Bone Regeneration Potential after Tumor Excision in Osteosarcoma Patients
by Max Baron, Philip Drohat, Brooke Crawford, Francis J. Hornicek, Thomas M. Best and Dimitrios Kouroupis
Bioengineering 2023, 10(10), 1187; https://doi.org/10.3390/bioengineering10101187 - 13 Oct 2023
Viewed by 1579
Abstract
Osteosarcoma (OS) is a type of bone cancer that is derived from primitive mesenchymal cells typically affecting children and young adults. The current standard of treatment is a combination of neoadjuvant chemotherapy and surgical resection of the cancerous bone. Post-resection challenges in bone [...] Read more.
Osteosarcoma (OS) is a type of bone cancer that is derived from primitive mesenchymal cells typically affecting children and young adults. The current standard of treatment is a combination of neoadjuvant chemotherapy and surgical resection of the cancerous bone. Post-resection challenges in bone regeneration arise. To determine the appropriate amount of bone to be removed, preoperative imaging techniques such as bone and CT scans are employed. To prevent local recurrence, the current standard of care suggests maintaining bony and soft tissue margins from 3 to 7 cm beyond the tumor. The amount of bone removed in an OS patient leaves too large of a deficit for bone to form on its own and requires reconstruction with metal implants or allografts. Both methods require the bone to heal, either to the implant or across the allograft junction, often in the setting of marrow-killing chemotherapy. Therefore, the issue of bone regeneration within the surgically resected margins remains an important challenge for the patient, family, and treating providers. Mesenchymal stem/stromal cells (MSCs) are potential agents for enhancing bone regeneration post tumor resection. MSCs, used with scaffolds and growth factors, show promise in fostering bone regeneration in OS cases. We spotlight two MSC types—bone marrow-derived (BM-MSCs) and adipose tissue-derived (ASCs)—highlighting their bone regrowth facilitation and immunomodulatory effects on immune cells like macrophages and T cells, enhancing therapeutic outcomes. The objective of this review is two-fold: review work demonstrating any ability of MSCs to target the deranged immune system in the OS microenvironment, and synthesize the available literature on the use of MSCs as a therapeutic option for stimulating bone regrowth in OS patients post bone resection. When it comes to repairing bone defects, both MB-MSCs and ASCs hold great potential for stimulating bone regeneration. Research has showcased their effectiveness in reconstructing bone defects while maintaining a non-tumorigenic role following wide resection of bone tumors, underscoring their capability to enhance bone healing and regeneration following tumor excisions. Full article
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