Mesenchymal stem/stromal cell-based therapy: mechanism, systemic safety and biodistribution for precision clinical applications

Zhuang, Wei-Zhan; Lin, Yiheng; Su, Long-Jyun; Wu, Meng-Shiue; Jeng, Han Yin; Chang, Huan‐Cheng; Huang, Yen-Hua; Ling, Thai-Yen

doi:10.1186/s12929-021-00725-7

Cited by 146 publications

(125 citation statements)

References 299 publications

(348 reference statements)

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“…Of all multipotent stem cells or adult cells, the ones presenting with the highest clinical application potential are the mesenchymal stem cells derived from adipose tissue, bone marrow, umbilical cord and placenta, due to their low immunogenicity, their immunomodulatory effect, and the fact that they do not induce an immunogenic response as they do not express the class II major histocompatibility complex (MHC-II) or T-lymphocyte costimulatory molecules such as CD40L, CD80 or CD86 [ 18 , 19 ].…”

Section: Advanced Therapies In Hemophiliamentioning

confidence: 99%

Gene Therapy in Hemophilia: Recent Advances

Rodríguez-Merchán

Pablo-Moreno

Liras

2021

IJMS

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Hemophilia is a monogenic mutational disease affecting coagulation factor VIII or factor IX genes. The palliative treatment of choice is based on the use of safe and effective recombinant clotting factors. Advanced therapies will be curative, ensuring stable and durable concentrations of the defective circulating factor. Results have so far been encouraging in terms of levels and times of expression using mainly adeno-associated vectors. However, these therapies are associated with immunogenicity and hepatotoxicity. Optimizing the vector serotypes and the transgene (variants) will boost clotting efficacy, thus increasing the viability of these protocols. It is essential that both physicians and patients be informed about the potential benefits and risks of the new therapies, and a register of gene therapy patients be kept with information of the efficacy and long-term adverse events associated with the treatments administered. In the context of hemophilia, gene therapy may result in (particularly indirect) cost savings and in a more equitable allocation of treatments. In the case of hemophilia A, further research is needed into how to effectively package the large factor VIII gene into the vector; and in the case of hemophilia B, the priority should be to optimize both the vector serotype, reducing its immunogenicity and hepatotoxicity, and the transgene, boosting its clotting efficacy so as to minimize the amount of vector administered and decrease the incidence of adverse events without compromising the efficacy of the protein expressed.

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Section: Advanced Therapies In Hemophiliamentioning

confidence: 99%

Gene Therapy in Hemophilia: Recent Advances

Rodríguez-Merchán

Pablo-Moreno

Liras

2021

IJMS

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“…On the other hand, umbilical cord mesenchymal stem cells (UC-MSCs) hold a higher proliferation with greater immunomodulation capacity. A review by Zhuang et al even shows MSCs as promising therapeutic strategy still shadowed with tumor initiation risk; UC-MSC however shows the highest tumor suppression properties compared to other MSCs and with the lowest tumor promotion effects compared to other types of MSCs [ 16 ]. These safety profiles have put UC-MSCs as another promising option to be the precursor of allogeneic MSCs in bone regeneration.…”

Section: Introductionmentioning

confidence: 99%

Integration of Umbilical Cord Mesenchymal Stem Cell Application in Hydroxyapatite-Based Scaffolds in the Treatment of Vertebral Bone Defect due to Spondylitis Tuberculosis: A Translational Study

Rahyussalim

Nugroho

Zufar

et al. 2021

Stem Cells International

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Background. Vertebral bone defect represents one of the most commonly found skeletal problems in the spine. Progressive increase of vertebral involvement of skeletal tuberculosis (TB) is reported as the main cause, especially in developed countries. Conventional spinal fusion using bone graft has been associated with donor-site morbidity and complications. We reported the utilization of umbilical cord mesenchymal stem cells (UC-MSCs) combined with hydroxyapatite (HA) based scaffolds in treating vertebral bone defect due to spondylitis tuberculosis. Materials and Methods. Three patients with tuberculous spondylitis in the thoracic, thoracolumbar, or lumbar region with vertebral body collapse of more than 50 percent were included. The patient underwent a 2-stage surgical procedure, consisting of debridement, decompression, and posterior stabilization in the first stage followed by anterior fusion using the lumbotomy approach at the second stage. Twenty million UC-MSCs combined with HA granules in 2 cc of saline were transplanted to fill the vertebral bone defect. Postoperative alkaline phosphatase level, quality of life, and radiological healing were evaluated at one-month, three-month, and six-month follow-up. Results. The initial mean ALP level at one-month follow-up was 48.33 ± 8.50 U / L . This value increased at the three-month follow-up but decreased at the six-month follow-up time, 97 ± 8.19 U / L and 90.33 ± 4.16 U / L , respectively. Bone formation of 50-75% of the defect site with minimal fracture line was found. Increased bone formation comprising 75-100% of the total bone area was reported six months postoperation. A total score of the SF-36 questionnaire showed better progression in all 8 domains during the follow-up with the mean total score at six months of 2912.5 ± 116.67 from all patients. Conclusion. Umbilical cord mesenchymal stem cells combined with hydroxyapatite-based scaffold utilization represent a prospective alternative therapy for bone formation and regeneration of vertebral bone defect due to spondylitis tuberculosis. Further clinical investigations are needed to evaluate this new alternative.

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“…The use of mesenchymal stromal cells (MSCs) is an emerging therapeutic strategy for the treatment of severely ill patients. MSCs have been studied in numerous medical conditions, and their immunomodulatory and regenerative potential is well documented [ 1 ]. MSCs are currently being used for two purposes which do not exclude one another, namely, immunomodulation and tissue regeneration [ 2 , 3 ].…”

Section: Introductionmentioning

confidence: 99%

Mesenchymal Stromal Cells: Potential Option for COVID-19 Treatment

Primorac

Čemerin

Matišić³

et al. 2021

Pharmaceutics

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The COVID-19 pandemic has significantly impacted the way of life worldwide and continues to bring high mortality rates to at-risk groups. Patients who develop severe COVID-19 pneumonia, often complicated with ARDS, are left with limited treatment options with no targeted therapy currently available. One of the features of COVID-19 is an overaggressive immune reaction that leads to multiorgan failure. Mesenchymal stromal cell (MSC) treatment has been in development for various clinical indications for over a decade, with a safe side effect profile and promising results in preclinical and clinical trials. Therefore, the use of MSCs in COVID-19-induced respiratory failure and ARDS was a logical step in order to find a potential treatment option for the most severe patients. In this review, the main characteristics of MSCs, their proposed mechanism of action in COVID-19 treatment and the effect of this therapy in published case reports and clinical trials are discussed.

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Mesenchymal stem/stromal cell-based therapy: mechanism, systemic safety and biodistribution for precision clinical applications

Cited by 146 publications

References 299 publications

Gene Therapy in Hemophilia: Recent Advances

Gene Therapy in Hemophilia: Recent Advances

Integration of Umbilical Cord Mesenchymal Stem Cell Application in Hydroxyapatite-Based Scaffolds in the Treatment of Vertebral Bone Defect due to Spondylitis Tuberculosis: A Translational Study

Mesenchymal Stromal Cells: Potential Option for COVID-19 Treatment

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