Modeling the Bone Marrow Microenvironment to Better Understand the Pathogenesis, Progression, and Treatment of Hematological Cancers
Simple Summary
Abstract
1. Hematological Malignancies
2. The Bone Marrow Niche Is a Complex and Heterogeneous Organ
3. Modeling the Bone Marrow Niche
3.1. Two-Dimensional Co-Cultures
3.2. Three-Dimensional Co-Cultures
3.2.1. Spheroids and Organoids
3.2.2. Importance of Scaffold Choice
3.2.3. Dynamic 3D Models
4. Important Considerations and Future Directions
5. Conclusions
Author Contributions
Funding
Data Availability Statement
Conflicts of Interest
Abbreviations
2D | Two-Dimensional |
3D | Three-Dimensional |
ALL | Acute Lymphoblastic Leukemia |
AML | Acute Myeloid Leukemia |
B-ALL | B-cell Acute Lymphoblastic Leukemia |
CLL | Chronic Lymphocytic Leukemia |
CML | Chronic Myeloid Leukemia |
DLBCL | Diffuse Large B-cell Lymphoma |
ECM | Extracellular Matrix |
HSC | Hematopoietic Stem Cell |
iPSC-BMO | Induced Pluripotent Stem-Cell-Derived Bone Marrow Organoids |
LSC | Leukemia Stem Cell |
MDS | Myelodysplastic Syndromes |
MM | Multiple Myeloma |
MPN | Myeloproliferative Neoplasms |
MSC | Mesenchymal Stem Cell |
PDMS | Polydimethylsiloxane |
T-ALL | T-cell Acute Lymphoblastic Leukemia |
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Summary of Model | Advantages | Limitations | Uses | References |
---|---|---|---|---|
Genetically modified | Physiologically relevant; same species; can examine the role of the immune system and native components in hematological malignancies | Expensive; not necessarily relevant to humans; not suitable for high-throughput drug screening | Pathogenesis; drug sensitivity | [32,39,40,41,42] |
Xenograft/implantation | May be physiologically relevant (if orthotopic or involving humanized ossicles); can examine role of multiple cell types simultaneously in physiologically relevant situations | Expensive; not necessarily equivalent to humans; cannot examine the role of the immune system; not suitable for high-throughput drug screening | Drug sensitivity; progression | [31,34,35,36,37,43] |
Summary of Model | Advantages | Limitations | Uses | References |
---|---|---|---|---|
Direct co-culture: cancer cells are grown directly on bone marrow stromal cell monolayers | Easy and inexpensive to establish; can study the effect of stromal cells on cancer cells and vice versa; can examine the impact of cell–cell contact; more relevant than 2D single-cell culture; allows the study of homogeneous populations | Does not contain multiple cell types; lacks 3D or anatomical factors associated with the niche; unable to perform downstream assays separately for each cell type; not possible to perform high-throughput assays for drug treatments | Examines cell biology and signaling processes involved in relapse and drug sensitivity (adhesion, migration, proliferation); allows the examination of drug sensitivity | [43,45,46,47,48,49,50] |
Indirect co-culture: cancer cells are grown indirectly with microenvironment cells separated by a permeable membrane or insert | Easy and inexpensive to establish; can study the effect of microenvironment cells on cancer cells and vice versa; allows the sharing of secreted factors through a permeable membrane; allows the study of homogeneous populations | Lacks cell–cell contact; does not contain multiple cell types; lacks 3D or anatomical factors associated with the niche; not possible to perform high-throughput assays for drug treatments | Examines signaling processes involved in bone marrow microenvironment; allows the examination of drug sensitivity | [51,52] |
Indirect co-culture (media): cancer or microenvironment cells are grown in conditioned media from another cell type | Easy and inexpensive to establish; can study the effect of secreted factors on different cell types; allows the study of homogeneous populations | Lacks cell–cell contact; does not contain multiple cell types; lacks 3D or anatomical factors associated with the niche | Allows the examination of drug sensitivity; examines the effect of secreted biomolecules on other cell types | [47] |
Model | Summary of Model | Advantages | Limitations | Uses | References |
---|---|---|---|---|---|
Static 3D co-culture | Scaffold-free: cancer and microenvironment cells are grown without a scaffold and are allowed to morph into spheroids/organoids in the absence of an anchor | More physiologically relevant than the 2D model; does not require specialized equipment; can study cell–cell interactions | Does not contain multiple cell types; lacks ECM–cancer cell interactions; time-consuming; grown under static conditions; not suitable for high-throughput drug screening | Examines signaling processes; drug sensitivity | [44,61,62,63,64,65,66,67,68,69,70,71,72,73,74,75,76] |
Scaffold-based: cancer and microenvironment cells are grown in the presence of a synthetic or biological scaffold and are allowed to grow as spheroids/organoids | More accurately recapitulates the bone marrow microenvironment; can study cell–cell and cell–ECM interactions | Time-consuming; expensive; grown under static conditions; not suitable for high-throughput drug screening | Examines signaling processes; drug sensitivity | ||
Dynamic 3D co-culture | Bioreactor: uses a 3D bioreactor to grow cancer cells, microenvironment cells, and scaffolds | Can examine multiple cell types; can study cell–cell and cell–ECM interactions; grown under dynamic conditions | Expensive and requires specialized equipment; time-consuming; dynamic growth conditions can disrupt cells or the scaffold architecture; not suitable for high-throughput drug screening | Examines signaling processes; drug sensitivity | [77,78] |
Microfluidics: uses a 3D bioreactor to grow cancer cells, microenvironment cells, and scaffolds (mimics osteoblastic and vascular niches) | Can examine multiple cell types; can examine multiple niches simultaneously; can study cell–cell and cell–ECM interactions; grown under dynamic conditions | Expensive and requires specialized equipment; time-consuming; dynamic growth conditions can disrupt cells or the scaffold architecture; not suitable for high-throughput drug screening | Model processes involved in progression and relapse; drug sensitivity | [79,80,81] |
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Skelding, K.A.; Barry, D.L.; Lincz, L.F. Modeling the Bone Marrow Microenvironment to Better Understand the Pathogenesis, Progression, and Treatment of Hematological Cancers. Cancers 2025, 17, 2571. https://doi.org/10.3390/cancers17152571
Skelding KA, Barry DL, Lincz LF. Modeling the Bone Marrow Microenvironment to Better Understand the Pathogenesis, Progression, and Treatment of Hematological Cancers. Cancers. 2025; 17(15):2571. https://doi.org/10.3390/cancers17152571
Chicago/Turabian StyleSkelding, Kathryn A., Daniel L. Barry, and Lisa F. Lincz. 2025. "Modeling the Bone Marrow Microenvironment to Better Understand the Pathogenesis, Progression, and Treatment of Hematological Cancers" Cancers 17, no. 15: 2571. https://doi.org/10.3390/cancers17152571
APA StyleSkelding, K. A., Barry, D. L., & Lincz, L. F. (2025). Modeling the Bone Marrow Microenvironment to Better Understand the Pathogenesis, Progression, and Treatment of Hematological Cancers. Cancers, 17(15), 2571. https://doi.org/10.3390/cancers17152571