Mesenchymal stromal cells: Putative microenvironmental modulators become cell therapy

Krampera, Mauro; Blanc, Katarina Le

doi:10.1016/j.stem.2021.09.006

Cited by 160 publications

(136 citation statements)

References 215 publications

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“…For more than a decade mesenchymal stromal/stem cells (MSC) have shown promising therapeutic properties in regenerative medicine [ 154 , 155 ]. MSC are multipotent cells with immunomodulatory properties [ 156 , 157 ] and are capable of self-renewal (to proliferate without losing their differentiation potential) [ 155 ]. They can be easily isolated from bone marrow (BM), adipose, and placental tissue.…”

Section: Stem Cell-based Therapeutic Approaches In Neonatal Lung and ...mentioning

confidence: 99%

Perinatal Hyperoxia and Developmental Consequences on the Lung-Brain Axis

Obst

Herz

Alcázar

et al. 2022

Oxidative Medicine and Cellular Longevity

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Approximately 11.1% of all newborns worldwide are born preterm. Improved neonatal intensive care significantly increased survival rates over the last decades but failed to reduce the risk for the development of chronic lung disease (i.e., bronchopulmonary dysplasia (BPD)) and impaired neurodevelopment (i.e., encephalopathy of prematurity (EoP)), two major long-term sequelae of prematurity. Premature infants are exposed to relative hyperoxia, when compared to physiological in-utero conditions and, if needed to additional therapeutic oxygen supplementation. Both are associated with an increased risk for impaired organ development. Since the detrimental effects of hyperoxia on the immature retina are known for many years, lung and brain have come into focus in the last decade. Hyperoxia-induced excessive production of reactive oxygen species leading to oxidative stress and inflammation contribute to pulmonary growth restriction and abnormal neurodevelopment, including myelination deficits. Despite a large body of studies, which unraveled important pathophysiological mechanisms for both organs at risk, the majority focused exclusively either on lung or on brain injury. However, considering that preterm infants suffering from BPD are at higher risk for poor neurodevelopmental outcome, an interaction between both organs seems plausible. This review summarizes recent findings regarding mechanisms of hyperoxia-induced neonatal lung and brain injury. We will discuss common pathophysiological pathways, which potentially link both injured organ systems. Furthermore, promises and needs of currently suggested therapies, including pharmacological and regenerative cell-based treatments for BPD and EoP, will be emphasized. Limited therapeutic approaches highlight the urgent need for a better understanding of the mechanisms underlying detrimental effects of hyperoxia on the lung-brain axis in order to pave the way for the development of novel multimodal therapies, ideally targeting both severe preterm birth-associated complications.

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Section: Stem Cell-based Therapeutic Approaches In Neonatal Lung and ...mentioning

confidence: 99%

Perinatal Hyperoxia and Developmental Consequences on the Lung-Brain Axis

Obst

Herz

Alcázar

et al. 2022

Oxidative Medicine and Cellular Longevity

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“…Cells derived from patient or donor tissues can be isolated and transplanted into defects to alter wound healing through direct mechanisms, differentiating and forming new tissues. Alternatively, transplanted cells can play indirect roles in tissue regeneration by secreting various signaling factors (236). In particular, mesenchymal stromal cells (MSCs) from oral (e.g., alveolar bone, gingiva, dental pulp, dental papilla, dental follicle, PDL) or extra-oral sources (adipose tissue, bone marrow, etc.)…”

Section: Cell Delivery and Recruitment Pdl Cell Transplantationmentioning

confidence: 99%

Periodontal Wound Healing and Regeneration: Insights for Engineering New Therapeutic Approaches

2022

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Periodontitis is a widespread inflammatory disease that leads to loss of the tooth supporting periodontal tissues. The few therapies available to regenerate periodontal tissues have high costs and inherent limitations, inspiring the development of new approaches. Studies have shown that periodontal tissues have an inherent capacity for regeneration, driven by multipotent cells residing in the periodontal ligament (PDL). The purpose of this review is to describe the current understanding of the mechanisms driving periodontal wound healing and regeneration that can inform the development of new treatment approaches. The biologic basis underlying established therapies such as guided tissue regeneration (GTR) and growth factor delivery are reviewed, along with examples of biomaterials that have been engineered to improve the effectiveness of these approaches. Emerging therapies such as those targeting Wnt signaling, periodontal cell delivery or recruitment, and tissue engineered scaffolds are described in the context of periodontal wound healing, using key in vivo studies to illustrate the impact these approaches can have on the formation of new cementum, alveolar bone, and PDL. Finally, design principles for engineering new therapies are suggested which build on current knowledge of periodontal wound healing and regeneration.

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“…Desirable properties and translational variables (e.g., product characterization parameters, time and mode of delivery, cryopreservation protocols, monitoring of the clinical response, and prediction of therapeutic success etc.) may have to be defined individually for each therapeutic cell product type [ 2 , 4 , 34 ], as done in this review.…”

Section: Introductionmentioning

confidence: 99%

“…While the HSCT approach is proven successful, it should be noted that HSPCs have extensive self-renewing properties and even a small number of “stem cells” can multiply and accomplish the desired hematopoietic reconstitution [ 25 ]. In contrast, MSCs differ substantially from HSPCs, since they appear to execute therapeutic properties mainly as “hit and run” mechanism without lifelong persistence or engraftment [ 34 ]. The cells are mainly thought to exert their therapeutic function by instructing host cells through paracrine signals, thereby initiating a healing cascade or by modulating the balance between inflammation and anti-inflammation [ 41 ].…”

Section: Introductionmentioning

confidence: 99%

Impact of Cryopreservation and Freeze-Thawing on Therapeutic Properties of Mesenchymal Stromal/Stem Cells and Other Common Cellular Therapeutics

et al. 2022

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Purpose of Review Cryopreservation and its associated freezing and thawing procedures–short “freeze-thawing”–are among the final steps in economically viable manufacturing and clinical application of diverse cellular therapeutics. Translation from preclinical proof-of-concept studies to larger clinical trials has indicated that these processes may potentially present an Achilles heel to optimal cell product safety and particularly efficacy in clinical trials and routine use. Recent Findings We review the current state of the literature on how cryopreservation of cellular therapies has evolved and how the application of this technique to different cell types is interlinked with their ability to engraft and function upon transfer in vivo, in particular for hematopoietic stem and progenitor cells (HSPCs), their progeny, and therapeutic cell products derived thereof. We also discuss pros and cons how this may differ for non-hematopoietic mesenchymal stromal/stem cell (MSC) therapeutics. We present different avenues that may be crucial for cell therapy optimization, both, for hematopoietic (e.g., effector, regulatory, and chimeric antigen receptor (CAR)-modified T and NK cell based products) and for non-hematopoietic products, such as MSCs and induced pluripotent stem cells (iPSCs), to achieve optimal viability, recovery, effective cell dose, and functionality of the cryorecovered cells. Summary Targeted research into optimizing the cryopreservation and freeze-thawing routines and the adjunct manufacturing process design may provide crucial advantages to increase both the safety and efficacy of cellular therapeutics in clinical use and to enable effective market deployment strategies to become economically viable and sustainable medicines.

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Mesenchymal stromal cells: Putative microenvironmental modulators become cell therapy

Cited by 160 publications

References 215 publications

Perinatal Hyperoxia and Developmental Consequences on the Lung-Brain Axis

Perinatal Hyperoxia and Developmental Consequences on the Lung-Brain Axis

Periodontal Wound Healing and Regeneration: Insights for Engineering New Therapeutic Approaches

Impact of Cryopreservation and Freeze-Thawing on Therapeutic Properties of Mesenchymal Stromal/Stem Cells and Other Common Cellular Therapeutics

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