R. Decker (San Diego, US)

Genomics Institute of the Novartis Research Foundation Musculoskeletal Regenerative Medicine

Presenter Of 1 Presentation

Extended Abstract (for invited Faculty only) Others

2.0.2 - Bridging the Bed-Bench Gap: Scientist Perspective

Presentation Number
2.0.2
Presentation Topic
Others
Lecture Time
13:20 - 13:40
Session Type
Plenary Session
Corresponding Author

Abstract

Introduction

It’s an exciting time for Orthoregeneration research. New tools and technologies have provided further insight into the biology and repair of joint tissues than ever before. Despite much progress in recent decades, the quest to achieve “perfect” joint restoration in patients with damaged cartilage has remained elusive. Perhaps the answer has been lost somewhere in translation. It is a long journey from bench to bedside, and this talk will explore why and how effective collaboration between basic scientists and physicians is essential to achieve our common goals.

Content

By definition, translational research leverages basic biology to create and implement practices which improve patient care [1]. Recent major advances in gene and cell therapy highlight how successful scientist-physician collaborations have resulted in ground-breaking therapies for patients [2, 3] and key examples exist in the cartilage repair field as well [4, 5]. A formidable obstacle to such partnerships is a perceived cultural divide between basic scientists and clinicians, which is not unique to the Orthoregeneration field [6]. This culture divide can often be attributed to communication barriers, and as highlighted by Restifo and Phelan, basic scientists and clinicians often do not speak the same language. [6] Lengthy and highly specialized training result in the creation of unique dialects including specific terminology and acronyms. These dialects separate not only the scientists and clinicians, but can alienate them from the general public as well. Where then, do we begin to bridge this divide? First, defining shared challenges and objectives is a critical step forward.

Fundamentally, both clinicians and basic scientists in our field are working to restore joint function. It is well understood from both perspectives that joints are complicated organs involving multiple tissues under varied stresses. However, there is less agreement regarding which specific challenges are the greatest in the field. At the bench, basic scientists have recently made great progress towards understanding signaling mechanisms required for maintenance of a healthy chrondrocyte phenotype [7]. We have new answers for long standing questions regarding the origin and fate of intrinsic joint progenitor cell populations [8-11]. If, how and when this information could be leveraged to develop new therapies for patients remains unknown. From a basic science perspective these are all intriguing areas of research – but which would be the highest priority for clinicians? Further communication is needed to develop a consensus.

Recent data suggests that the traditional linear pipeline from bench to bedside may not be the most efficient path forward [12]. Basic scientists in the Orthoregeneration field need a clear understanding of which issues clinicians view as the greatest challenges. Inversely, clinicians could benefit from information about the knowledge and tools available from the bench. A refined circular or iterative model of translational research which fosters greater reciprocal interaction between scientists and clinicians could be the most productive path forward towards these efforts [12]. Furthermore, this model should strive to include not only experts in the Orthoregeneration field, but interdisciplinary collaborations as well [13].

In summary, several key challenges exist for basic science – clinical collaborations. There is great strength in the diversity between scientists and clinicians. To leverage this strength, the Orthoregeneration field must work towards speaking a common language, collectively defining challenges so that we may work together to achieve shared goals.

References

1. Woolf, S.H., The meaning of translational research and why it matters. Jama, 2008. 299(2): p. 211-213.

2. Mendell, J.R., et al., Single-Dose Gene-Replacement Therapy for Spinal Muscular Atrophy. N Engl J Med, 2017. 377(18): p. 1713-1722.

3. June, C.H., et al., CAR T cell immunotherapy for human cancer. Science, 2018. 359(6382): p. 1361-1365.

4. Grande, D.A., et al., The repair of experimentally produced defects in rabbit articular cartilage by autologous chondrocyte transplantation. Journal of Orthopaedic Research, 1989. 7(2): p. 208-218.

5. Brittberg, M., et al., Treatment of deep cartilage defects in the knee with autologous chondrocyte transplantation. New england journal of medicine, 1994. 331(14): p. 889-895.

6. Restifo, L.L. and G.R. Phelan, The cultural divide: exploring communication barriers between scientists and clinicians. Disease models & mechanisms, 2011. 4(4): p. 423-426.

7. Sherwood, J., Osteoarthritis year in review 2018: biology. Osteoarthritis and Cartilage, 2019. 27(3): p. 365-370.

8. Li, L., et al., Superficial cells are self-renewing chondrocyte progenitors, which form the articular cartilage in juvenile mice. The FASEB Journal, 2016. 31(3): p. 1067-1084.

9. Decker, R.S., et al., Cell origin, volume and arrangement are drivers of articular cartilage formation, morphogenesis and response to injury in mouse limbs. Developmental Biology, 2017. 426(1): p. 56-68.

10. Roelofs, A.J., et al., Joint morphogenetic cells in the adult mammalian synovium. Nature Communications, 2017. 8: p. 15040.

11. Fellows, C.R., et al., Characterisation of a divergent progenitor cell sub-populations in human osteoarthritic cartilage: the role of telomere erosion and replicative senescence. Scientific reports, 2017. 7: p. 41421.

12. Fudge, N., et al., Optimising Translational Research Opportunities: A Systematic Review and Narrative Synthesis of Basic and Clinician Scientists' Perspectives of Factors Which Enable or Hinder Translational Research. PloS one, 2016. 11(8): p. e0160475-e0160475.

13. Chao, H.-T., L. Liu, and H.J. Bellen, Building dialogues between clinical and biomedical research through cross-species collaborations. Seminars in cell & developmental biology, 2017. 70: p. 49-57.

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Moderator Of 2 Sessions

Plaza B&C Special Session
Session Type
Special Session
Date
06.10.2019
Time
15:15 - 16:15
Location
Plaza B&C
Plaza B&C Free Paper Session
Session Type
Free Paper Session
Date
08.10.2019
Time
10:30 - 12:00
Location
Plaza B&C

Meeting Participant of

Turner - ICRS Board Room (15) ICRS Committee Meeting

Basic Science Committee