From Neuronal Differentiation of iPSCs to 3D Neuro-Organoids: Modelling and Therapy of Neurodegenerative Diseases

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.

Neural precursors cells expanded in a 3D micro-engineered niche present enhanced therapeutic efficacy in vivo

“…This is also relevant and in agreement with recent findings highlighting the importance of xeno-free biomaterials composition in SCs culture in vitro [66,67]. Few studies investigated the potentiality of scaffolds and SCs in the treatment of Parkinson's Disease (PD) [7,68,69]. Carlson and colleagues developed three-dimensional microtopographic scaffolds using tunable electrospun polymeric substrates with pluripotent stem cell-derived neurons [69,70].…”

“…Stem cells (SCs) show a great potential in therapeutics for restoring and regenerating native tissues, due to their ability to commit to different types of functional cells [1,2]. The development of therapies based on SCs is of key importance especially for diseases in which physiological tissue repair does not occur, including neurodegenerative diseases such as Parkinson's disease (PD) [3,4], spinal cord injuries [5,6] and amyotrophic lateral sclerosis [7,8]. In these diseases, restorative therapies based on neural cell replacement using embryonic stem (ES) cellderived neural cells have shown efficacy in animal models [9][10][11][12] but the clinical translation of therapies involving ES cells is generally opposed by medicines agencies, due to the risk of teratoma [13].…”

Recent Overview of the Use of iPSCs Huntington’s Disease Modeling and Therapy

“…Furthermore, HD-iPSC-NPCs can organize into three-dimensional (3D) organoids mimicking the architecture of brain tissue. In addition, iPSC-derived HD models represent a much more suitable alternative for drug screening and toxicity testing than widely used animal models [15,32]. Table 2.…”

Microphysiological Systems for Neurodegenerative Diseases in Central Nervous System

“…Adapting these two technologies to the neural MPS together will make it possible to reconstruct a more complex structure of the CNS. In addition to the neural MPSs, organoids for neural tissue are also emerging for neurodegenerative disease since it can recapitulate complex structure of the neural tissue [ 134 , 135 , 136 , 137 ]. In this way, studying neurodegenerative disease in vitro using several technical methods will be a way to get closer to the solution for ND.…”