Overcoming immunological barriers in regenerative medicine

Zakrzewski, Johannes L.; Brink, Marcel R.M. van den; Hubbell, Jeffrey A.

doi:10.1038/nbt.2960

Cited by 118 publications

(100 citation statements)

References 122 publications

(101 reference statements)

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“…Mesenchymal stromal cells (MSC) are widely used for tissue engineering applications because of their capacity to promote tissue regeneration (Zakrzewski et al 2014) while modulating immune responses (Prockop and Oh 2012). Currently, there are more than 300 registered clinical trials (www.clinicaltrials.gov) in which MSC are used to treat several different diseases, with applications ranging from bone and cartilage repair to spinal cord, cardiac, and bladder regeneration (Kramer et al 2012).…”

Section: Introductionmentioning

confidence: 99%

Long term morphological characterization of mesenchymal stromal cells 3D spheroids built with a rapid method based on entry-level equipment

et al. 2016

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Three-dimensional (3D) spheroids of mesenchymal stromal cells (MSC) have been demonstrated to improve a wide range of MSC features, such as multilineage potential, secretion of therapeutic factors, and resistance against hypoxic condition. Accordingly, they represent a promising tool in regenerative medicine for several biological and clinical applications. Many approaches have been proposed to generate MSC spheroids. They usually require specific generation systems, such as rotatory bioreactors or low-attachment plates, and each approach has its own disadvantages. Furthermore, an over-time analysis of morphological homogeneity and architectural stability of the spheroids generated is rarely provided. In this work we adapted the ''pellet culture'' method to obtain homogenous spheroids of MSC and maintain them in vitro for long term studies. We analysed their outer and inner structure over a 2-month period to provide morphological and architectural information regarding the spheroids generated. Quantitative and qualitative data were obtained using brightfield and confocal microscope imaging coupled to a computational analysis to estimate volume, sphericity, and jagging degree. In addition, histological evaluation was performed to more thoroughly assess the cellular composition and the internal architecture of the 3D spheroids. The results provided show that MSC spheroids generated with the proposed approach are homogeneous and stable, from both morphological and architectural points of view, for a period of at least 15 days, approximately between day 15 and day 30 after their generation. Accordingly, the approach proposed serves as a rapid, cost-effective, and efficient method to generate and maintain MSC spheroids using common entry-level laboratory equipment only.Keywords Mesenchymal stromal/stem cells Á 3D multicellular spheroids Á Pellet culture method Á Morphological analysis Á Microscopy Á Computational analysis Chiara Bellotti and Serena Duchi contributed equally to this work.

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Section: Introductionmentioning

confidence: 99%

Long term morphological characterization of mesenchymal stromal cells 3D spheroids built with a rapid method based on entry-level equipment

et al. 2016

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“…[16][17][18][19] Understanding the direct immunosuppressive effect of nanoparticles and resultant development of new immunosuppressive therapies can impact both pharmaceutical and regenerative medicine technologies. 9,20,21 When developing methods to suppress immune response, it is important to consider both innate and adaptive immune responses. Innate immunity involves the first response activation of macrophages and neutrophils that secrete specific cytokines, which produce local inflammation at the site of reaction.…”

Section: Introductionmentioning

confidence: 99%

Nanoparticles and direct immunosuppression

Ngobili

Daniele

2016

Exp Biol Med (Maywood)

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Targeting the immune system with nanomaterials is an intensely active area of research. Specifically, the capability to induce immunosuppression is a promising complement for drug delivery and regenerative medicine therapies. Many novel strategies for immunosuppression rely on nanoparticles as delivery vehicles for small-molecule immunosuppressive compounds. As a consequence, efforts in understanding the mechanisms in which nanoparticles directly interact with the immune system have been overshadowed. The immunological activity of nanoparticles is dependent on the physiochemical properties of the nanoparticles and its subsequent cellular internalization. As the underlying factors for these reactions are elucidated, more nanoparticles may be engineered and evaluated for inducing immunosuppression and complementing immunosuppressive drugs. This review will briefly summarize the state-of-the-art and developments in understanding how nanoparticles induce immunosuppressive responses, compare the inherent properties of nanomaterials which induce these immunological reactions, and comment on the potential for using nanomaterials to modulate and control the immune system.

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“…Some of them are closer to clinical testing than others, but all represent promising advances in the field of transplantation tolerance. More information on these and other approaches can be found in several recent reviews [2,3].…”

Section: State Of the Fieldmentioning

confidence: 99%