Human Bone Marrow Organoids for Disease Modeling, Discovery, and Validation of Therapeutic Targets in Hematologic Malignancies

Zidi

et al. 2023

Cells

Spheroids and organoids are important novel players in medical and life science research. They are gradually replacing two-dimensional (2D) cell cultures. Indeed, three-dimensional (3D) cultures are closer to the in vivo reality and open promising perspectives for academic research, drug screening, and personalized medicine. A large variety of cells and tissues, including tumor cells, can be the starting material for the generation of 3D cultures, including primary tissues, stem cells, or cell lines. A panoply of methods has been developed to generate 3D structures, including spontaneous or forced cell aggregation, air–liquid interface conditions, low cell attachment supports, magnetic levitation, and scaffold-based technologies. The choice of the most appropriate method depends on (i) the origin of the tissue, (ii) the presence or absence of a disease, and (iii) the intended application. This review summarizes methods and approaches for the generation of cancer spheroids and organoids, including their advantages and limitations. We also highlight some of the challenges and unresolved issues in the field of cancer spheroids and organoids, and discuss possible therapeutic applications.

Section: Current Source To Generate and Culture In Vitro Tumor Sphero...mentioning

confidence: 99%

Section: Current Source To Generate and Culture In Vitro Tumor Sphero...mentioning

confidence: 99%

Cancer Spheroids and Organoids as Novel Tools for Research and Therapy: State of the Art and Challenges to Guide Precision Medicine

Zidi

et al. 2023

Cells

“…Last but not least, iPSC-derived HSPCs can also be used to recapitulate the hematopoietic bone marrow, a microenvironment where homing, proliferation, and differentiation of HSCs take place. This establishment of the HSC niche within organoids has recently been demonstrated by Khan et al [100]. They argued that bone marrow organoids mimicking the central bone marrow space could be generated with iPSCs that were embedded in mixed-matrix hydrogels.…”

Section: Recapitulation Of Immune System Within the Organoid: A Platf...mentioning

confidence: 74%

Induced pluripotent stem cell-derived hematopoietic stem and progenitor cells: potential, challenges, and future perspectives

Han

Kim

2023

Organoid

Hematopoietic stem and progenitor cells (HSPCs) are responsible for the lifetime dynamics of hematopoiesis, as they are well known for their self-renewing ability and multipotency to differentiate into all types of blood cells, including both myeloid and lymphoid lineages. However, due to their limited amount and accessibility, there is a strong need to search out alternative methods to produce HSPCs. In this review, we suggest induced pluripotent stem cells (iPSCs) as a new viable source for HSPC production because these cells have the potential to self-renew while being relatively easy to modify. Recent studies have revealed that the recapitulation of definitive hematopoiesis is the key to the successful in vitro production of HSPCs with multilineage potential. Therefore, we summarized recent progress in establishing the generation of definitive HSPCs with high maturity and functionality in vitro. Definitive HSPCs can be used in disease modeling and gene therapy for genetic blood disorders via gene modification in iPSCs, applied in cellular immunotherapy in the form of a universal chimeric antigen receptor system, and may recapitulate the intricate immune system within the iPSC-derived organoids that closely mimic the in vivo pathophysiological environment. In summary, this review provides an overview of the generation of HSPCs from iPSCs, in terms of the developmental process of hematopoiesis, in vitro attempts to produce iPSC-derived definitive HSPCs, and the following applications of these cells in numerous areas. This review sheds light on the concept of iPSC-derived definitive HSPCs, setting a milestone for artificial blood production in the near future.

“…A 14-day expansion increased CD34 + cell numbers by 30.1-fold and reduced time for haematopoietic recovery, but showed an impaired engraftment ability. More recently, a 3D MSC culture system composed of multicellular spheroids embedded in extracellular matrix has been shown to mimic the functionality of BM niche cells, maintain the expression of stem cell markers and release haematopoietic maintenance factors [ 75 , 76 ]. These approaches show promise as an in vitro tool to study the microenvironment in which HSCs reside.…”

Section: In Vitro Maintenance and Expansion Of Hspcsmentioning

confidence: 99%

In Vitro Human Haematopoietic Stem Cell Expansion and Differentiation

Bozhilov

Hsu

Brown

et al. 2023

Cells

The haematopoietic system plays an essential role in our health and survival. It is comprised of a range of mature blood and immune cell types, including oxygen-carrying erythrocytes, platelet-producing megakaryocytes and infection-fighting myeloid and lymphoid cells. Self-renewing multipotent haematopoietic stem cells (HSCs) and a range of intermediate haematopoietic progenitor cell types differentiate into these mature cell types to continuously support haematopoietic system homeostasis throughout life. This process of haematopoiesis is tightly regulated in vivo and primarily takes place in the bone marrow. Over the years, a range of in vitro culture systems have been developed, either to expand haematopoietic stem and progenitor cells or to differentiate them into the various haematopoietic lineages, based on the use of recombinant cytokines, co-culture systems and/or small molecules. These approaches provide important tractable models to study human haematopoiesis in vitro. Additionally, haematopoietic cell culture systems are being developed and clinical tested as a source of cell products for transplantation and transfusion medicine. This review discusses the in vitro culture protocols for human HSC expansion and differentiation, and summarises the key factors involved in these biological processes.