Injectable Systems for Intra-Articular Delivery of Mesenchymal Stromal Cells for Cartilage Treatment: A Systematic Review of Preclinical and Clinical Evidence

Abstract

Stem cell-based therapy is a promising approach to treat cartilage lesions and clinical benefits have been reported in a number of studies. However, the efficacy of cell injection procedures may be impaired by cell manipulation and damage as well as by cell dissemination to non-target tissues. To overcome such issues, mesenchymal stromal cell (MSC) delivery may be performed using injectable vehicles as containment systems that further provide a favorable cell microenvironment. The aim of this systematic review was to analyze the preclinical and clinical literature on platelet-rich plasma (PRP), hyaluronic acid (HA), and hydrogels for the delivery of MSCs. The systematic literature search was performed using the PubMed and Web of science databases with the following string: “(stem cells injection) AND (platelet rich plasma OR PRP OR platelet concentrate OR biomaterials OR hyaluronic acid OR hydrogels)”: 40 studies (19 preclinical and 21 clinical) met the inclusion criteria. This review revealed an increasing interest on the use of injectable agents for MSC delivery. However, while negligible adverse events and promising clinical outcomes were generally reported, the prevalence of low quality studies hinders the possibility to demonstrate the real benefits of using such injectable systems. Specific studies must be designed to clearly demonstrate the added benefits of these systems to deliver MSCs for the treatment of cartilage lesions and osteoarthritis.

dvances of hyaluronic acid in stem cell therapy and tissue engineering, including current clinical trials

“…The development of articular stem cell therapies is promising, since these cells have the ability for self-renewal and differentiation into osteogenic or chondrogenic lineages (Canadas et al, 2018). HA injection therapies, combined with MSCs from BM, are currently under investigation for bone and cartilage tissue regeneration (Kaleka et al, 2018;Roffi et al, 2018), (Fig. 7).…”

Therapies for osteoarthritis today and tomorrow: Review

“…To minimise those issues, injectors sought different injectable vehi-cles as containment systems to provide a better microenvironment for injected cells. Roffi et al 12 reviewed 40 studies (19 preclinical and 21 clinical trials) with platelet-rich plasma (PRP), hyaluronic acid (HA) and hydrogels to help delivery and function of MSC. Even though the authors reported negligible adverse events and promising clinical outcomes, the prevalence of low-quality studies prevented demonstration of benefit, calling for studies designed to more clearly demonstrate possible improved outcomes.…”

Combining canine mesenchymal stromal cells and hyaluronic acid for cartilage repair

“…The association of MSCs with HA to treat cartilage has been studied in different species, mostly animal models. Although the treatments are safe and promising results are observed, it is still not possible to draw conclusions on their real benefits, due to the limitations inherent to artificial models and to the heterogeneity and low quality of many of the clinical studies (Roffi et al, 2018). It has been stressed that the use of naturally occurring diseases in companion animals can provide more reliable information in translational medicine (Kol et al, 2015;Hoffman and Dow, 2016).…”