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Continuing Challenges in Advancing Preclinical Science in Skeletal Cell-Based Therapies and Tissue Regeneration.

ABSTRACT: Cell-based therapies hold much promise for musculoskeletal medicine; however, this rapidly growing field faces a number of challenges. Few of these therapies have proven clinical benefit, and an insufficient regulatory environment has allowed for widespread clinical implementation without sufficient evidence of efficacy. The technical and biological complexity of cell-based therapies has contributed to difficulties with reproducibility and mechanistic clarity. In order to aid in addressing these challenges, we aim to clarify the key issues in the preclinical cell therapy field, and to provide a conceptual framework for advancing the state of the science. Broadly, these suggestions relate to: (i) delineating cell-therapy types and moving away from "catch-all" terms such as "stem cell" therapies; (ii) clarifying descriptions of cells and their processing; and (iii) increasing the standard of in vivo evaluation of cell-based therapy experiments to determining cell fates. Further, we provide an overview of methods for experimental evaluation, data sharing, and professional society participation that would be instrumental in advancing this field. © 2018 American Society for Bone and Mineral Research.

SUBMITTER: Featherall J

PROVIDER: S-EPMC6691896 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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Continuing Challenges in Advancing Preclinical Science in Skeletal Cell-Based Therapies and Tissue Regeneration.

Featherall Joseph J Robey Pamela G PG Rowe David W DW

Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 20180904 10

Cell-based therapies hold much promise for musculoskeletal medicine; however, this rapidly growing field faces a number of challenges. Few of these therapies have proven clinical benefit, and an insufficient regulatory environment has allowed for widespread clinical implementation without sufficient evidence of efficacy. The technical and biological complexity of cell-based therapies has contributed to difficulties with reproducibility and mechanistic clarity. In order to aid in addressing these ...[more]

PMID: 30133922

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Project description:BACKGROUND:Periodontal tissue regeneration (PTR) is the ultimate goal of periodontal therapy. Currently, stem cell therapy is considered a promising strategy for achieving PTR. However, there is still no conclusive comparison that distinguishes clear hierarchies among different kinds of stem cells. METHODS:A systematic review and network meta-analysis (NMA) was performed using MEDLINE (via PubMed), EMBASE, and Web of Science up to February 2020. Preclinical studies assessing five types of stem cells for PTR were included; the five types of stem cells included periodontal ligament-derived stem cells (PDLSCs), bone marrow-derived stem cells (BMSCs), adipose tissue-derived stem cells (ADSCs), dental pulp-derived stem cells (DPSCs), and gingival-derived stem cells (GMSCs). The primary outcomes were three histological indicators with continuous variables: newly formed alveolar bone (NB), newly formed cementum (NC), and newly formed periodontal ligament (NPDL). We performed pairwise meta-analyses using a random-effects model and then performed a random-effects NMA using a multivariate meta-analysis model. RESULTS:Sixty preclinical studies assessing five different stem cell-based therapies were identified. The NMA showed that in terms of NB, PDLSCs (standardized mean difference 1.87, 95% credible interval 1.24 to 2.51), BMSCs (1.88, 1.17 to 2.59), and DPSCs (1.69, 0.64 to 2.75) were statistically more efficacious than cell carriers (CCs). In addition, PDLSCs were superior to GMSCs (1.49, 0.04 to 2.94). For NC, PDLSCs (2.18, 1.48 to 2.87), BMSCs (2.11, 1.28 to 2.94), and ADSCs (1.55, 0.18 to 2.91) were superior to CCs. For NPDL, PDLSCs (1.69, 0.92 to 2.47) and BMSCs (1.41, 0.56 to 2.26) were more efficacious than CCs, and PDLSCs (1.26, 0.11 to 2.42) were superior to GMSCs. The results of treatment hierarchies also demonstrated that the two highest-ranked interventions were PDLSCs and BMSCs. CONCLUSION:PDLSCs and BMSCs were the most effective and well-documented stem cells for PTR among the five kinds of stem cells evaluated in this study, and there was no statistical significance between them. To translate the stem cell therapies for PTR successfully in the clinic, future studies should utilize robust experimental designs and reports.

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Dataset Information

Continuing Challenges in Advancing Preclinical Science in Skeletal Cell-Based Therapies and Tissue Regeneration.

Publications

Continuing Challenges in Advancing Preclinical Science in Skeletal Cell-Based Therapies and Tissue Regeneration.

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