A review and update for registered clinical studies of stem cells for non-tumorous and non-hematological diseases

Despite the recent explosion of investigations on dental pulp regeneration using various tissue engineering strategies, the translation of the findings from such studies into therapeutic applications has not been properly achieved. The purpose of this scoping review was to systematically review the efficacy of mesenchymal stem cell transplantation for dental pulp regeneration. A literature search was conducted using five electronic databases from their inception to January 2021 and supplemented by hand searches. A total of 17 studies, including two clinical trials and 15 animal studies using orthotopic pulp regeneration models, were included for the review. The risk of bias for the individual studies was assessed. This scoping review demonstrated that the regeneration of vascularized pulp-like tissue was achieved using the stem cell transplantation strategy in animal models. Autologous cell transplantation in two clinical studies also successfully regenerated vascularized vital tissue. Dental pulp stem cell subpopulations, such as mobilized dental pulp stem cells, injectable scaffolds such as atelocollagen, and a granulocyte-colony forming factor, were the most commonly used for pulp regeneration. The overall risk of bias was unclear for animal studies and was moderate or judged to raise some concerns for clinical studies. More high-quality clinical studies are needed to further determine the safety and efficacy of the stem cell transplantation strategy for dental pulp regeneration.

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Effectiveness of Biologic Factors in Shoulder Disorders

The Open Orthopaedics Journal ◽

10.2174/1874325001711010163 ◽

2017 ◽

Vol 11 (1) ◽

pp. 163-182 ◽

Cited By ~ 4

Author(s):

Dimitrios Giotis ◽

Ashkan Aryaei ◽

Theofanis Vasilakakos ◽

Nikolaos K. Paschos

Keyword(s):

Stem Cells ◽

Growth Factors ◽

Clinical Studies ◽

Platelet Rich Plasma ◽

Repair Process ◽

Poor Quality ◽

Loss Of Function ◽

Shoulder Disorders ◽

Biologic Factors

Background:Shoulder pathology can cause significant pain, discomfort, and loss of function that all interfere with activities of daily living and may lead to poor quality of life. Primary osteoarthritis and rotator cuff diseases with its sequalae are the main culprits. Management of shoulder disorders using biological factors gained an increasing interest over the last years. This interest reveals the need of effective treatments for shoulder degenerative disorders, and highlights the importance of a comprehensive and detailed understanding of the rapidly increasing knowledge in the field.Methods:This study will describe most of the available biology-based strategies that have been recently developed, focusing on their effectiveness in animal and clinical studies.Results:Data fromin vitrowork will also be briefly presented; in order to further elucidate newly acquired knowledge regarding mechanisms of tissue degeneration and repair that would probably drive translational work in the next decade. The role of platelet rich-plasma, growth factors, stem cells and other alternative treatments will be described in an evidence-based approach, in an attempt to provide guidelines for their clinical application. Finally, certain challenges that biologic treatments face today will be described as an initiative for future strategies.Conclusion:The application of different growth factors and mesenchymal stem cells appears as promising approaches for enhancing biologic repair. However, data from clinical studies are still limited, and future studies need to improve understanding of the repair process in cellular and molecular level and evaluate the effectiveness of biologic factors in the management of shoulder disorders.

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Adipose-Derived Mesenchymal Stem Cells in the Treatment of Diabetic Foot Ulcers: A Review of Preclinical and Clinical Studies

Angiology ◽

10.1177/0003319720939467 ◽

2020 ◽

Vol 71 (9) ◽

pp. 853-863 ◽

Cited By ~ 2

Author(s):

Francisco Javier Álvaro-Afonso ◽

Irene Sanz-Corbalán ◽

José Luis Lázaro-Martínez ◽

Despoina Kakagia ◽

Nikolaos Papanas

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Diabetic Foot ◽

Clinical Studies ◽

Optimal Dose ◽

Arterial Disease ◽

Therapeutic Angiogenesis ◽

Foot Ulcers ◽

Diabetic Foot Ulcers ◽

Safe Alternative

This review provides an outline of the use of adipose-derived mesenchymal stem cells (AMSCs) in the treatment of diabetic foot ulcers (DFUs). A systematic search of PubMed and the Cochrane database was performed on October 2, 2019. Eighteen studies were identified (14 preclinical and 4 clinical). Studies in animal models have demonstrated that AMSCs enhance diabetic wound healing, accelerate granulation tissue formation, and increase reepithelialization and neovascularization. Only 1 randomized control trial has been published so far. Patients (n = 25) with DFUs were treated using an allogeneic AMSC directly on the wound bed as a primary dressing, and improvements were found in complete wound closure in the treatment group (n = 16). Three clinical studies showed that autologous AMSC might be a safe alternative to achieve therapeutic angiogenesis in patients with diabetes and peripheral arterial disease. Based on the available evidence, AMSCs hold promise in the treatment of DFUs. However, this evidence requires confirmation by well-designed trials. Additional studies are also required to understand some issues regarding this treatment for DFUs. For example, the potential application of autologous or allogeneic AMSCs in different types of DFUs, optimal dose/infusion schedules, safety evaluations, and cost-effectiveness.

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Mesenchymal Stem Cell Therapy in Stroke: A Systematic Review of Literature in Pre-Clinical and Clinical Research

Cell Transplantation ◽

10.1177/0963689718806846 ◽

2018 ◽

Vol 27 (12) ◽

pp. 1723-1730 ◽

Cited By ~ 19

Author(s):

Haiqing Zheng ◽

Bin Zhang ◽

Pratik Y. Chhatbar ◽

Yi Dong ◽

Ali Alawieh ◽

...

Keyword(s):

Systematic Review ◽

Stem Cells ◽

Stem Cell ◽

Cell Therapy ◽

Stem Cell Therapy ◽

Clinical Studies ◽

Animal Studies ◽

Current Evidence ◽

Human Trials

Exogenous stem cell therapy (SCT) has been recognized recently as a promising neuroregenerative strategy to augment recovery in stroke survivors. Mesenchymal stem cells (MSCs) are the primary source of stem cells used in the majority of both pre-clinical and clinical studies in stroke. In the absence of evidence-based guidelines on the use of SCT in stroke patients, understanding the progress of MSC research across published studies will assist researchers and clinicians in better achieving success in translating research. We conducted a systematic review on published literature using MSCs in both pre-clinical studies and clinical trials between 2008 and 2017 using the public databases PubMed and Ovid Medline, and the clinical trial registry ( www.clinicaltrials.gov ). A total of 78 pre-clinical studies and eight clinical studies were identified. While majority of the pre-clinical and clinical studies demonstrated statistically significant effects, the clinical significance of these findings was still unclear. Effect sizes could not be measured mainly due to reporting issues in pre-clinical studies, thus limiting our ability to compare results across studies quantitatively. The overall quality of both pre-clinical and clinical studies was sub-optimal. By conducting a systematic review of both pre-clinical and clinical studies on MSCs therapy in stroke, we assessed the quality of current evidence and identified several issues and gaps in translating animal studies to human trials. Addressing these issues and incorporating changes into future animal studies and human trials may lead to better success of stem cells-based therapeutics in the near future.

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Mesenchymal Stem Cells and Articular Cartilage Repair: Clinical Studies and Future Direction

The Open Orthopaedics Journal ◽

10.2174/1874325001105010296 ◽

2011 ◽

Vol 5 (1) ◽

pp. 296-301 ◽

Cited By ~ 17

Author(s):

Shahid Punwar

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Articular Cartilage ◽

Cartilage Repair ◽

Clinical Studies ◽

Articular Cartilage Repair ◽

Future Direction

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O.1 Pre-clinical studies with human adult mesenchymal stem-cells: What have we learned?

Neuromuscular Disorders ◽

10.1016/j.nmd.2011.06.757 ◽

2011 ◽

Vol 21 (9-10) ◽

pp. 640

Author(s):

M. Zatz ◽

N.M. Vieira ◽

M. Valadares ◽

M. Secco ◽

E. Zucconi ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Clinical Studies ◽

Human Adult ◽

Adult Mesenchymal Stem Cells

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Immunotherapy with dendritic cells loaded with glioblastoma stem cells: from preclinical to clinical studies

Cancer Immunology Immunotherapy ◽

10.1007/s00262-015-1754-9 ◽

2015 ◽

Vol 65 (1) ◽

pp. 101-109 ◽

Cited By ~ 28

Author(s):

Gaetano Finocchiaro ◽

Serena Pellegatta

Keyword(s):

Stem Cells ◽

Dendritic Cells ◽

Clinical Studies ◽

Glioblastoma Stem Cells

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Stem cells in the heart: What's the buzz all about? Part 2: Arrhythmic risks and clinical studies

Heart Rhythm ◽

10.1016/j.hrthm.2008.02.011 ◽

2008 ◽

Vol 5 (6) ◽

pp. 880-887 ◽

Cited By ~ 39

Author(s):

Rachel Ruckdeschel Smith ◽

Lucio Barile ◽

Elisa Messina ◽

Eduardo Marbán

Keyword(s):

Stem Cells ◽

Clinical Studies

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New Frontiers or the Treatment of Interstitial Cystitis/Bladder Pain Syndrome - Focused on Stem Cells, Platelet-Rich Plasma, and Low-Energy Shock Wave

International Neurourology Journal ◽

10.5213/inj.2040104.052 ◽

2020 ◽

Vol 24 (3) ◽

pp. 211-221 ◽

Cited By ~ 2

Author(s):

Chih-Chieh Lin ◽

Yun-Ching Huang ◽

Wei-Chia Lee ◽

Yao-Chi Chuang

Keyword(s):

Stem Cells ◽

Regenerative Medicine ◽

Interstitial Cystitis ◽

Clinical Studies ◽

Platelet Rich Plasma ◽

Pain Syndrome ◽

Bladder Pain Syndrome ◽

Low Energy ◽

Preclinical Studies ◽

Bladder Pain

Interstitial cystitis/bladder pain syndrome (IC/BPS), which is characterized by bladder pain and irritative voiding symptoms, is a frustrating disease without effective treatment. The cause is still largely not understood, although urothelium ischemia/hypoxia, apoptosis, denudation, and infiltration of inflammatory cells are common histopathological findings. The current uncertainty regarding the etiology and pathology of IC/BPS has a negative impact on its timely and successful treatment; therefore, the development of new treatment modalities is urgently needed. Herein, we present advances in our knowledge on this topic and review the potential application of regenerative medicine for the treatment of IC/BPS. This article provides information on the basic characteristics and clinical evidence of stem cells, platelet-rich plasma (PRP), and low-energy shock waves (LESWs) based on a literature review with a search strategy for articles related to IC/BPS, stem cells, PRP, and LESW published in MEDLINE and PubMed. Stem cells, PRP, and LESW, which modulate inflammatory processes and promote tissue repair, have been proven to improve bladder regeneration, relieve bladder pain, inhibit bladder inflammation, and increase bladder capacity in some preclinical studies. However, clinical studies are still in their infancy. Based on the mechanisms of action of stem cells, PRP, and LESW documented in many preclinical studies, the potential applications of regenerative medicine for the treatment of IC/BPS is an emerging frontier of interest. However, solid evidence from clinical studies remains to be obtained.

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