Cell Therapies for Tendon: Treatments and Regenerative Medicine

Grognuz, Anthony; Aeberhard, Pierre‐Arnaud; Michetti, Murielle; Hirt‐Burri, Nathalie; Scaletta, Corinne; Roessingh, Anthony de Buys; Raffoul, Wassim; Laurent-Applegate, Lee Ann

doi:10.1007/978-3-030-19962-3_27

Cited by 3 publications

(4 citation statements)

References 109 publications

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“…Despite large acquired experience and hindsight, it appears that pure surgical management of tendinous affections remains unsatisfactory for appropriate healing. Therefore, applied and translational research has been prompting the development of additional or complementary therapeutic solutions such as cell-based therapies [ 8 , 9 , 17 ].…”

Section: Discussionmentioning

confidence: 99%

“…Therein, additive or synergistic combinations of surgical intervention and cell-based therapies may prove to be essential for optimization of clinical outcomes. Due to specificities of tendon tissues (i.e., vascularization, dynamic force transmission, collagen fiber micro- and macro-structures), many considered therapeutic approaches to date have fallen short of clinician and patient expectations with regard to healing outcomes [ 8 , 9 , 10 , 11 ].…”

Section: Introductionmentioning

confidence: 99%

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Industrial Development of Standardized Fetal Progenitor Cell Therapy for Tendon Regenerative Medicine: Preliminary Safety in Xenogeneic Transplantation

et al. 2021

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Tendon defects require multimodal therapeutic management over extensive periods and incur high collateral burden with frequent functional losses. Specific cell therapies have recently been developed in parallel to surgical techniques for managing acute and degenerative tendon tissue affections, to optimally stimulate resurgence of structure and function. Cultured primary human fetal progenitor tenocytes (hFPT) have been preliminarily considered for allogeneic homologous cell therapies, and have been characterized as stable, consistent, and sustainable cell sources in vitro. Herein, optimized therapeutic cell sourcing from a single organ donation, industrial transposition of multi-tiered progenitor cell banking, and preliminary preclinical safety of an established hFPT cell source (i.e., FE002-Ten cell type) were investigated. Results underlined high robustness of FE002-Ten hFPTs and suitability for sustainable manufacturing upscaling within optimized biobanking workflows. Absence of toxicity or tumorigenicity of hFPTs was demonstrated in ovo and in vitro, respectively. Furthermore, a 6-week pilot good laboratory practice (GLP) safety study using a rabbit patellar tendon partial-thickness defect model preliminarily confirmed preclinical safety of hFPT-based standardized transplants, wherein no immune reactions, product rejection, or tumour formation were observed. Such results strengthen the rationale of the multimodal Swiss fetal progenitor cell transplantation program and prompt further investigation around such cell sources in preclinical and clinical settings for musculoskeletal regenerative medicine.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Industrial Development of Standardized Fetal Progenitor Cell Therapy for Tendon Regenerative Medicine: Preliminary Safety in Xenogeneic Transplantation

et al. 2021

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“…Among the possible alterations to normal tissular functions are perturbations of nerve function and vascularization, cell density and phenotypes changes, cell–cell interactions, cell–matrix interactions, cytokine balance, and overall tendon matrix alterations ( Figure 3 ) [ 5 , 64 ]. Based on the high complexity of tendon-specific pathologies and healing process, an autologous biological-based therapeutic approach (e.g., PRP injections) appears to be an optimal management option [ 65 , 66 ]. PRP is easily available in standard clinical settings and contains a variety of bioactive factors, such as PDGF, TGF, VEGF, IGF, or EGF, which are known to be actively involved in tissue healing [ 23 , 67 , 68 ].…”

Section: Discussionmentioning

confidence: 99%

Process Optimization and Efficacy Assessment of Standardized PRP for Tendinopathies in Sports Medicine: Retrospective Study of Clinical Files and GMP Manufacturing Records in a Swiss University Hospital

et al. 2023

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Platelet-rich plasma (PRP) preparations have recently become widely available in sports medicine, facilitating their use in regenerative therapy for ligament and tendon affections. Quality-oriented regulatory constraints for PRP manufacturing and available clinical experiences have underlined the critical importance of process-based standardization, a pre-requisite for sound and homogeneous clinical efficacy evaluation. This retrospective study (2013–2020) considered the standardized GMP manufacturing and sports medicine-related clinical use of autologous PRP for tendinopathies at the Lausanne University Hospital (Lausanne, Switzerland). This study included 48 patients (18–86 years of age, with a mean age of 43.4 years, and various physical activity levels), and the related PRP manufacturing records indicated a platelet concentration factor most frequently in the range of 2.0–2.5. The clinical follow-up showed that 61% of the patients reported favorable efficacy outcomes (full return to activity, with pain disappearance) following a single ultrasound-guided autologous PRP injection, whereas 36% of the patients required two PRP injections. No significant relationship was found between platelet concentration factor values in PRP preparations and clinical efficacy endpoints of the intervention. The results were in line with published reports on tendinopathy management in sports medicine, wherein the efficacy of low-concentration orthobiologic interventions appears to be unrelated to sport activity levels or to patient age and gender. Overall, this study confirmed the effectiveness of standardized autologous PRP preparations for tendinopathies in sports medicine. The results were discussed in light of the critical importance of protocol standardization for both PRP manufacturing and clinical administration to reduce biological material variability (platelet concentrations) and to enhance the robustness of clinical interventions (comparability of efficacy/patient improvement).

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“…Vast arrays of potential therapeutic cell types have been investigated in tendon bioengineering for regeneration enhancement, including tendon sheath fibroblasts, adult tenocytes, stem cells, placenta cells, amniotic cells, and platelet-derivatives (Kadner et al, 2002;Kaviani et al, 2002Kaviani et al, , 2003Awad et al, 2003;Chen et al, 2009;Akhundov et al, 2012;Xu et al, 2013;Petrou et al, 2014). Tendon FPCs present tremendous therapeutic potential due to high stability of their tenogenic and karyotypic properties in culture, low propensity for dedifferentiation, expansion characteristics, therapeutic stimulatory potential, and the ability to maintain cell viability along with rheological properties of bioengineered hydrogel constructs (Grognuz et al, 2019). Their similarities with stem cells but lack of specific tendon markers require in vitro characterization of tendon FPCs using marker panels (e.g., type I collagen, scleraxis, and tenomodulin) (Hulmes, 2002;Le Blanc et al, 2003;Docheva et al, 2005;Murchison et al, 2007;Banos et al, 2008;Taylor et al, 2009).…”

Section: Phenotypic Stability Chondrogenic Potential and Biomechanicsmentioning

confidence: 99%

Holistic Approach of Swiss Fetal Progenitor Cell Banking: Optimizing Safe and Sustainable Substrates for Regenerative Medicine and Biotechnology

Laurent

Hirt‐Burri

Scaletta

et al. 2020

Front. Bioeng. Biotechnol.

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Swiss Fetal Progenitor Cell Banking is proposed, achieving sustained standards and potential production of billions of affordable and efficient therapeutic doses. Thereby, the aim is to validate the core therapeutic value proposition, to increase awareness and use of standardized protocols for translational regenerative medicine, potentially impacting millions of patients suffering from cutaneous and musculoskeletal diseases. Alternative applications of FPC banking include biopharmaceutical therapeutic product manufacturing, thereby indirectly and synergistically enhancing the power of modern therapeutic armamentariums. It is hypothesized that a single qualifying fetal organ donation is sufficient to sustain decades of scientific, medical, and industrial developments, as technological optimization and standardization enable high efficiency.

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Cell Therapies for Tendon: Treatments and Regenerative Medicine

Cited by 3 publications

References 109 publications

Industrial Development of Standardized Fetal Progenitor Cell Therapy for Tendon Regenerative Medicine: Preliminary Safety in Xenogeneic Transplantation

Industrial Development of Standardized Fetal Progenitor Cell Therapy for Tendon Regenerative Medicine: Preliminary Safety in Xenogeneic Transplantation

Process Optimization and Efficacy Assessment of Standardized PRP for Tendinopathies in Sports Medicine: Retrospective Study of Clinical Files and GMP Manufacturing Records in a Swiss University Hospital

Holistic Approach of Swiss Fetal Progenitor Cell Banking: Optimizing Safe and Sustainable Substrates for Regenerative Medicine and Biotechnology

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