Mixed Cells, Not Stem Cells

Rules of the Road for Mixed Cell Therapies

At the end of the two-day meeting which included a patient panel, the experts called for universal nomenclature standards for cellular therapies and biologics, standards for measuring and reporting the composition of these therapies and their clinical outcomes and establishing registries and clinical trial networks to accelerate rigorous assessment and optimization of regenerative therapies for musculoskeletal diseases.

Specifically:

• “The use of the term stem cells to describe minimally manipulated cell preparations is problematic and has created substantial confusion for patients, physicians, and the general public.”
  • Therefore: Refer to minimally manipulated cell products and tissue derived culture-expanded cells as “cell therapy” not ‘stem cell’ therapy.
  • And: Inform patients that these therapies are largely untested and uncharacterized.
• “Unlike conventional pharmaceuticals where a known concentration of a bioactive substance is administered to achieve a targeted biological effect, most biologics are complex mixtures of variable composition that are not easily assayed.” Blood products such as PRP and minimally manipulated autologous cell preparations lack consistent standards and the biological status of the donor and the preparation methods vary widely.
  • Therefore: Minimum information for studies reporting biologics (MIBO) checklists be used as a guide for study design and reporting (see link above for the checklist details).
  • And: For PRP and cell-based therapies, the MIBO should include specific items which were also listed in the symposium report (link above).
• “Address the variability in outcomes by identifying the biologic targets (e.g., cell proliferation, anti-inflammatory, antifibrotic effect) for PRP. This is needed to more precisely choose the optimal PRP formulation to focus treatment for each specific tissue and to ultimately reduce this variability. As an example, for rotator cuff tendon repair, the primary targets are considered to be provision of signaling molecules that drive cellular differentiation to reform the organized structure of the enthesis.

Absence of Evidence Isn’t Necessarily Evidence of Absence

There wouldn’t be substantial patient demand for biologic treatment of painful knees, shoulders, feet and other inflamed articulating sections of the musculoskeletal system if cell-based biologic therapies didn’t work on some level.

So, to paraphrase an old saying, absence of evidence isn’t necessarily evidence of absence.

Dr. Chu emphasizes that: “All of us are excited about the potential benefits of stem cells to treating some of our toughest clinical problems such as knee osteoarthritis and to potentially regenerate damaged and aging tissues. Our goals were to provide a consensus framework for delivering evidence-based care—so that patients are informed and protected from unproven treatments and that clinical practice be conducted in a way that does not compromise the development and introduction of well characterized new cell therapies in the future.”

This excellent symposium, in effect, showed how to bridge the gap between cell therapy evidence and marketing.

It delivered a clear impact agenda for improving the way we speak about these therapies, the way we clinically evaluate them and how we get to a place where physicians can use and optimize biologics in orthopedics—reliably and safely.

Kudos to all the symposium participants including, notably, Fei Wang, Ph.D. from the NIH and Erin Ransford AAOS Manager of Research Advocacy.

Here is the link to the symposium agenda.

The symposium’s consensus statement authors and/or editors were:

[1]Department of Orthopaedics, Rush University Medical School

[2]Department of Orthopaedic Surgery, Duke University Medical School

[3]Department of Orthopaedics, Rush University Medical School

ⁱChu CR, Rodeo S, Bhutani N, et al: “Optimizing Clinical Use of Biologics in Orthopaedic Surgery: Consensus Recommendations from the 2018 AAOS/NIH U-13 Conference

ⁱⁱStem Cell Basics I  Accessed July 17, 2018