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Review Article
DOI: 10.1016/j.reumae.2020.10.001
Available online 4 May 2021
Expanded Mesenchymal Stromal Cells in knee osteoarthritis: A systematic literature review
Tratamiento de la artrosis de rodilla con células mesenquimales estromales expandidas: revisión sistemática de la literatura
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Paloma Álvarez Hernández, José de la Mata Llord
Corresponding author
drdelamata@institutoari.com

Corresponding author.
Instituto de Salud Osteoarticular ARI, Madrid, Spain
Received 13 July 2020. Accepted 15 October 2020
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Table 2. Summary of evidence
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Abstract
Objective

To analyse the efficacy and safety of intra-articular injection of expanded Mesenchymal Stromal Cells (MSCs) in knee osteoarthritis.

Methods

Systematic Literature Review. A pre-defined search strategy was run in Medline, Embase and Cochrane Library until February 2018. Inclusion criteria: knee osteoarthritis (grades II-IV Kellgren-Lawrence); intra-articular injection of MSCs (without surgical co-treatments); Randomized Controlled Trials (RCTs) or Quasi-experimental Clinical Trials (QCTs) N ≥ 10 and ≥6 months of follow-up were included. Evidence was assigned according to the Scottish Intercollegiate Guidelines Network (SIGN).

Results

The search identified 252 articles. Nine proof-of-concept trials (3 RCTs, 6 QCTs) were included (N = 169). Evidence showed clinical improvement in 60% of patients. Structural benefit was reported in half of patients. Clinical benefit was observed from the 3rd month and structural improvement from the 6th. All studies reported maximum clinical and structural benefit a year following the implant. This benefit was sustained for up to 24 months. Studies with doses ≥40 × 106 showed more consistent clinical and structural benefits than those with lower doses. No systemic adverse reactions were reported. The most common adverse effect was pain and/or inflammation in the puncture area (13–53%). The use of donor cells was as safe as autologous implants.

Conclusions

Intra-articular implants of MSCs seem to be safe with no serious adverse effects. Low-quality evidence precludes conclusions regarding efficacy in this review. However, the clinical and structural benefits observed provide a rationale for using expanded MSCs implants in osteoarthritis patients. High-quality evidence trials are needed to further determine best protocols to maximize clinical and structural improvement.

Keywords:
Mesenchymal Stromal Cells
Knee osteoarthritis
Intra-articular treatment
Systematic literature review
Resumen
Objetivo

Analizar la eficacia y la seguridad de los implantes de células mesenquimales estromales expandidas (MSCs, por sus siglas en inglés) en la artrosis de rodilla.

Métodos

Revisión sistemática de la literatura. Estrategia de búsqueda en Medline, Embase y Cochrane Library hasta febrero del 2018. Inclusión: artrosis de rodilla (II-IV Kellgren); inyección intra-articular de MSCs; ensayos controlados aleatorizados (ECA) y ensayos clínicos cuasi-experimentales (ECC) ≥ 6 meses y N ≥ 10.

Resultados

De 252 artículos identificados, se incluyeron 3 ECA y 6 ECC (N = 169). El 60% de los pacientes mejoraron clínicamente y el 50% estructuralmente hasta 2 años después del implante. El beneficio máximo se alcanzó al año con dosis ≥40 × 106 MSCs. La intervención fue bien tolerada, igualmente segura en implantes alogénicos y autólogos.

Conclusiones

Las MSCs intra-articulares son seguras. La baja calidad de la evidencia analizada no admite conclusiones sobre la eficacia, pero prueba un fundamento para su uso en la artrosis como modificador de síntoma y de estructura que debe ser constatado en ensayos de alta calidad.

Palabras clave:
Células mesenquimales estromales
Células madre
Artrosis de rodilla
Tratamiento intra-articular
Revisión sistemática

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