U54HL165445

Multimodal Histologic Atlas of Human Bone Marrow - Project Summary

Overall, bone marrow produces blood cells whose functions range from oxygen delivery to anti-microbial defense to hemostasis, all originating from hematopoietic stem cells (HSC). To sustain and regulate this process, bone marrow stromal cells form multiple niche microenvironments, each tailored to the needs of a particular developing blood cell population.

Using highly-multiplexed imaging technologies, our proposed Bone Marrow Tissue Mapping Center (TMC) aims to systematically and quantitatively dissect the cellular composition and spatial organization of human bone marrow microenvironments. The resulting detailed maps will serve as an open and global platform for understanding which cells and interactions are critical for each branch of hematopoietic maturation, and how these vary by anatomical site and across diverse patient demographics.

The TMC will define cellular identities and cell states at the transcriptional, translational, and post-translational levels using NanoString DSP, multiplexed ion beam imaging (MIBI), and MALDI-MSI, which generate quantitative spatial maps of RNA, protein, and N-glycans, respectively. Our cross-disciplinary team not only includes the inventors of MIBI and a pioneer of MALDI-MSI, but also experts in human HSCs and human hematopoiesis, and a practicing hematopathologist with expertise in histopathologic bone marrow diagnosis.

To overcome the unique challenges of working with hard, mineralized bone, we will leverage parallel, robust, clinically-validated bone marrow processing pipelines which maximize and standardize sample quality and compatibility with current and future technologies. Integrating seamlessly into standard clinical workflows, our pipelines enable convenient sharing of prospectively-collected materials with the tissue core.

Samples will be collected from three different sources: (1) prospective, patient-matched multi-site collection from deceased donors to examine differences between anatomical sites, (2) prospective collection of femoral head from hip arthroplasty specimens for differences between age ranges, (3) iliac crest bone in the Stanford Pathology Archive for differences between races and genders. These multiple collection strategies, multiple sites, and different investigational focuses complement prior HUBMAP projects.

The data analysis core team has pioneered multiple novel data processing pipelines, including pixel-based analyses, cell-based analyses including state-of-the-art cell segmentation and cell clustering and enumeration, and neighborhood analyses. These tools are broadly applicable to all highly-multiplexed quantitative imaging technologies.

Overall, our team and strategy are exceedingly well-suited for executing the vision of the proposed Bone Marrow TMC. The spatial structure of bone marrow reflects the evolutionary mechanisms that terraformed bone to create unique microenvironments meeting the nutritional needs of developing blood cells with divergent functions. The interdependence between bone marrow tissue structure and hematopoiesis is informative not just in blood cell maturation, but for understanding metabolism, aging, and development of cellular therapies.

The Leland Stanford Junior University

THE DIVISION OF BLOOD DISEASES AND RESOURCES SUPPORTS RESEARCH AND RESEARCH TRAINING ON THE PATHOPHYSIOLOGY, DIAGNOSIS, TREATMENT, AND PREVENTION OF NON-MALIGNANT BLOOD DISEASES, INCLUDING ANEMIAS, SICKLE CELL DISEASE, THALASSEMIA, LEUKOCYTE BIOLOGY, PRE-MALIGNANT PROCESSES SUCH AS MYELODYSPLASIA AND MYELOPROLIFERATIVE DISORDERS, HEMOPHILIA AND OTHER ABNORMALITIES OF HEMOSTASIS AND THROMBOSIS, AND IMMUNE DYSFUNCTION. FUNDING ENCOMPASSES A BROAD SPECTRUM OF HEMATOLOGIC INQUIRY, RANGING FROM STEM CELL BIOLOGY TO MEDICAL MANAGEMENT OF BLOOD DISEASES AND TO ASSURING THE ADEQUACY AND SAFETY OF THE NATION'S BLOOD SUPPLY. PROGRAMS ALSO SUPPORT THE DEVELOPMENT OF NOVEL CELL-BASED THERAPIES TO BRING THE EXPERTISE OF TRANSFUSION MEDICINE AND STEM CELL TECHNOLOGY TO THE REPAIR AND REGENERATION OF HUMAN TISSUES AND ORGANS. SMALL BUSINESS INNOVATION RESEARCH (SBIR) PROGRAM: TO STIMULATE TECHNOLOGICAL INNOVATION, USE SMALL BUSINESS TO MEET FEDERAL RESEARCH AND DEVELOPMENT NEEDS, FOSTER AND ENCOURAGE PARTICIPATION IN INNOVATION AND ENTREPRENEURSHIP BY SOCIALLY AND ECONOMICALLY DISADVANTAGED PERSONS, AND INCREASE PRIVATE-SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT FUNDING. SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAM: TO STIMULATE TECHNOLOGICAL INNOVATION, FOSTER TECHNOLOGY TRANSFER THROUGH COOPERATIVE R&D BETWEEN SMALL BUSINESSES AND RESEARCH INSTITUTIONS, AND INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL R&D.

93.310 - Trans-NIH Research Support

National Heart Lung and Blood Institute (NHLBI) [HHS - NIH]

National Institute of Allergy and Infectious Diseases (NIAID) [HHS - NIH]

Stanford, California 94305 United States

Single Zip Code

Tissue Mapping Centers for the Human BioMolecular Atlas Program (U54 Clinical Trial Not Allowed) (RFA-RM-21-026)

Amendment Since initial award the End Date has been shortened from 07/31/26 to 06/30/26 and the total obligations have increased 293% from $1,500,000 to $5,888,084.