Abstract
In the last decade, the advances made into the reprogramming of somatic cells into induced pluripotent stem cells (iPSCs) led to great improvements towards their use as models of diseases. In particular, in the field of neurodegenerative diseases, iPSCs technology allowed to culture in vitro all types of patient-specific neural cells, facilitating not only the investigation of diseases’ etiopathology, but also the testing of new drugs and cell therapies, leading to the innovative concept of personalized medicine. Moreover, iPSCs can be differentiated and organized into 3D organoids, providing a tool which mimics the complexity of the brain’s architecture. Furthermore, recent developments in 3D bioprinting allowed the study of physiological cell-to-cell interactions, given by a combination of several biomaterials, scaffolds, and cells. This technology combines bio-plotter and biomaterials in which several types of cells, such as iPSCs or differentiated neurons, can be encapsulated in order to develop an innovative cellular model. IPSCs and 3D cell cultures technologies represent the first step towards the obtainment of a more reliable model, such as organoids, to facilitate neurodegenerative diseases’ investigation. The combination of iPSCs, 3D organoids and bioprinting will also allow the development of new therapeutic approaches. Indeed, on the one hand they will lead to the development of safer and patient-specific drugs testing but, also, they could be developed as cell-therapy for curing neurodegenerative diseases with a regenerative medicine approach.
Highlights
Stem cells represent a very versatile cell source, as they are able to undergo a very high number of divisions thanks to their self-renewal property and differentiate into almost all adult cell types thanks to their pluripotency characteristic [1]
In the last few years, advances have been made to move on from a 2D to a 3D approach in order to gain further insights into the cytoarchitecture of the brain and into the disease mechanisms that may take place in the central nervous system. Both methods present with advantages and disadvantages: while 2D models with directed monolayer differentiation may provide an easier substrate for imaging assays and morphological studies such as dendrite complexity, 3D cultures can result in a large diversity of cell types and allow the study of cell-cell interactions between different populations [45,46]. 3D human brain cultures are usually obtained with the differentiation of induced pluripotent stem cells (iPSCs) into either neural cell aggregates or into more complex brain organoids
Two groundbreaking discoveries, i.e., somatic cells reprogramming into iPSCs and 3D bioprinting, changed the way of modeling diseases, in particular for those pathologies difficult to study in a simple cell culture, such as neurodegenerative diseases
Summary
Stem cells represent a very versatile cell source, as they are able to undergo a very high number of divisions thanks to their self-renewal property and differentiate into almost all adult cell types thanks to their pluripotency characteristic [1]. The use of stem cells research was limited, due to invasively harvesting techniques, such as through the bone marrow, adipose tissue extraction by liposuction or blood apheresis [2]. ].FFuurrththeerrmmoorree,, iiPPSSCCss ccaann bbeerreepprrooggrarmammmededfrofrmomanaynsyomsoamticatcicellcelilnl eli,ne, alloawlloinwginaglaeslessisnivnavsaisviveerreettrriieevvaall aannddpprroovvididiningga anenwewwawy atoysttoudsytuddiysedasiesse’amseesc’hmaneicshmasnwishmicshwarheich areppaatiteiennt-ts-psepceicfiicfi, co, poepneinnigngtotothtehesos-oc-aclaleldledpepresrosnoanliazleidzemd emdeicdinicein(eFi(gFuirgeur1e).1T).oTfourftuhretrheardavdanvcaence towtoawrdasrdtshitshidsirdeicrteicotino,ni,tiwt willillbebceocommeeininccrreeaassiinnggllyy nneecceessssaarryyttoofufulllylyuunndderesrtsatnadndthtehpeapthaothgeongiecnic mechanisms underlying neurodegenerative diseases. Human iPSCs provide a unique opportunity to mechanisms underlying neurodegenerative diseases. Human iPSCs provide a unique opportunity to fill in some knowledge gaps, such as the genotype-phenotype association of certain fill nineusoromdeegkennoewralteidvegedigsaepasse, ssu[6c]h. Many iPSCs’ lines have been generated from patients with neurodegenerative diseases, such as Alzheimer’s disease (AD) [9], Parkinson’s disease (PD) [10], Amyotrophic Lateral Sclerosis (ALS) [11], and Huntington’s disease (HD) [12]
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