Off the Shelf Cellular Therapeutics: Factors to Consider During Cryopreservation and Storage of Human Cells for Clinical Use

Woods, E.; Thirumala, S.; Badhe-Buchanan, S.; Clarke, D.; Mathew, Aby J.

doi:10.1016/j.jcyt.2016.03.146

Cited by 25 publications

(28 citation statements)

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“…Cell transplantation has gained significant momentum and initial cell products have reached the clinics . A critical component for most cell transplantation products is the use of cryopreservation, and therefore, the effects of cryopreservation have been well studied . The effect of cryopreservation on MSCs and hematopoietic stem cells, related to the potential as cell therapy products, overall demonstrates a minimal effect on cell viability and bioactivity.…”

Section: Discussionmentioning

confidence: 99%

Discogenic cell transplantation directly from a cryopreserved state in an induced intervertebral disc degeneration canine model

et al. 2018

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A multitude of studies has indicated the potential of cell therapy as a method for intervertebral disc (IVD) regeneration. Transplantation of a variety of cells has been assessed and shown capable of deterring the rate of degeneration in animal models and in human clinical trials. In this study, a novel approach using human discogenic nucleus pulposus cells directly from their cryopreserved state was assessed. In an established canine disc degeneration model, the degeneration process was evaluated in IVDs receiving precultured discogenic cells, thawedonly discogenic cells, and a saline sham injection after induction of degeneration. Degeneration progression was followed over time by the evaluation of the disc height index (DHI). Finally, after 12 weeks, the manipulated and control discs were explanted, histologically stained, and of the estimated 632 million low back pain patients globally will advance to a chronic condition. 1,2 Together, these compelling numbers engender a critical social-economic burden on society. For example, within the USA, 100 billion USD is spent annually on low back pain associated costs. 3,4 Currently, treatment options are limited and fail to restore or halt further advancement of the underlying pathology. 5 Degeneration of the intervertebral disc (IVD) is widely considered to be a predominant cause of low back pain. IVD degeneration is hallmarked by a dysregulation in extracellular matrix (ECM) homeostasis. 6,7 The exact origin of IVD degeneration remains to be elucidated; however, the nucleus pulposus (NP) is believed to be the place of onset. 8,9 Progression of IVD degeneration is characterized by a decline in proteoglycan production, an increase in matrix degenerative proteins, and a switch from type II collagen to type I collagen production. 6,7 Moreover, NP cells undergo senescence and dedifferentiation toward a more fibrotic phenotype. 10 The NP disorganization and height loss causes incorrect loading of adhering tendons promoting reorganization of tendon ECM to thicker and stiffer structures, further disrupting the mechanical features along the spine.

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Section: Discussionmentioning

confidence: 99%

Discogenic cell transplantation directly from a cryopreserved state in an induced intervertebral disc degeneration canine model

et al. 2018

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“…Using this protocol, the amount of available ad‐MVF was reduced by 37% after cryopreservation. This may be due to freeze‐thaw‐induced cell injury, which is induced by multiple mechanisms, including intracellular ice crystal formation, cytotoxic effects of the cryoprotectant and metabolic imbalances due to temperature‐dependent reactions (Woods, Thirumala, Badhe‐Buchanan, Clarke, & Mathew, ). In line with this explanation, we detected significantly higher numbers of necrotic cells within cryopreserved ad‐MVF.…”

Section: Discussionmentioning

confidence: 99%

Effects of cryopreservation on adipose tissue‐derived microvascular fragments

Laschke

Karschnia

Scheuer

et al. 2017

J Tissue Eng Regen Med

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Adipose tissue-derived microvascular fragments (ad-MVF) are effective vascularization units for tissue engineering. They rapidly reassemble into new microvascular networks after seeding on scaffolds and subsequent in vivo implantation. Herein, we analyzed whether the vascularization capacity of ad-MVF is affected by cryopreservation. Ad-MVF were isolated from the epididymal fat pads of C57BL/6 mice and cryopreserved for 7 days to compare their morphology, viability, cellular composition, and protein expression with freshly isolated control ad-MVF. Moreover, cryopreserved and control ad-MVF from green fluorescent protein (GFP) donor mice were seeded on collagen-glycosaminoglycan matrices (Integra ), which were implanted into dorsal skinfold chambers of GFP recipient animals to study their vascularization and incorporation using intravital fluorescence microscopy, histology, and immunohistochemistry. Cryopreservation of ad-MVF did not affect vessel morphology and cellular composition. However, cryopreservation was associated with an increased rate of necrotic cells and a significantly reduced number of transplantable ad-MVF. This was compensated by a higher angiogenic activity of the remaining ad-MVF, as indicated by significantly elevated expression levels of pro-angiogenic factors when compared to controls. Accordingly, cryopreserved and control ad-MVF induced a comparable vascularization and incorporation of implanted Integra without differences in microvascular network formation, maturation, and remodeling. Enhanced angiogenic sprouting even resulted in a higher fraction of GFP microvessels within the implants of the cryopreservation group. These findings indicate that cryopreservation of ad-MVF is feasible and, thus, offers the exciting opportunity to build up stocks of readily available vascularization units for future tissue engineering applications.

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“…Como é universalmente aceito, a água é o componente essencial para quase todos os processos biológicos, e sua remoção durante a formação de gelo submete a célula a desafi os extremos. Desta forma, sabe-se que existem diversos mecanismos de lesão nas celular mal compreendidos, contudo é possível enumerar os principais eventos a serem debelados para se obter uma criopreservação com alta taxa de sobrevivência, como a intolerância osmótica, toxicidade dos crioprotetores, lesão por resfriamento ou choque frio associada com a redução da temperatura de nucleação e lesão associada à mudança de fase águagelo até um estado vítreo, conforme fi gura 1 (MOTTA et al, 2014;WOODS et al, 2016;BAUST et al, 2017). Cohen et al (1985).…”

Section: Processos De Criopreservação E Seus Componentesunclassified

Biotecnologia Como Ferramenta Para O Conhecimento E Conservação Da Fauna E Flora Amazônica

Vidal¹,

Chaves²,

Silva³

2019

Genética E Melhoramento De Plantas E Animais

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Off the Shelf Cellular Therapeutics: Factors to Consider During Cryopreservation and Storage of Human Cells for Clinical Use

Cited by 25 publications

References 0 publications

Discogenic cell transplantation directly from a cryopreserved state in an induced intervertebral disc degeneration canine model

Discogenic cell transplantation directly from a cryopreserved state in an induced intervertebral disc degeneration canine model

Effects of cryopreservation on adipose tissue‐derived microvascular fragments

Biotecnologia Como Ferramenta Para O Conhecimento E Conservação Da Fauna E Flora Amazônica

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