Autologous Bone Marrow Transplantation for treatment of Multiple Sclerosis - Endogenous Hematopoietic Stem Cell Activation?

Purpose | Our study seeks to contribute novel insights into the development of novel HSC-based regenerative strategies for multiple sclerosis (MS) using our recently defined connection point between peripheral and-CNS immunity. We aim to develop a better mechanistic understanding of this autologous cell therapy, keeping clinical translation in mind, thereby offering new hope for individuals affected by MS and potentially other autoimmune disorders.

Expected results | The data will help assess the safety and viability of aHSCT and endogenous HSC activation as potential treatments for MS. Findings will highlight opportunities to optimize these treatment strategies for better efficacy. The results will provide a solid foundation for further research into these and related therapeutic approaches.

Innovation | This project is novel as it combines HSC expertise and novel HSC transplantation approaches with a classic neuroinflammation disease, such as MS. A novel aspect is also that we will use this newly identified niche, to study interactions between immune stem cells and autoimmune cells.

Significance | Building on our interdisciplinary expertise, our project aims to make significant contributions to the understanding of cell transplantation as a treatment of MS. We plan to fill crucial knowledge gaps and advance new treatment protocols through autologous HSCT and endogenous HSC activation using read-outs in the newly identified vulnerable niche.  Success of this project will be a step towards enabling us to bring innovative cell-based therapies into routine clinical practice for those with MS.

IGNITE Fellow - Kelley M. Swanberg

Kelley M. Swanberg, Ph.D. is a biomedical engineer who specializes in the methods and applications of ultra-high-field (7+ tesla) clinical and preclinical in vivo proton magnetic resonance spectroscopy (¹H MRS) and imaging (MRI). She received her B.A. in Neurobiology from Harvard University in Cambridge, MA, USA; her M.Sc. in East-West Medicine, Korean Medicine from Kyung Hee University in Seoul, South Korea; and her M.Sc. and Ph.D. in Biomedical Engineering from Columbia University in New York, NY, USA.

Since beginning her career in magnetic resonance (MR) at the Yale School of Medicine Magnetic Resonance Research Center (MRRC) in 2015, Dr. Swanberg has been methodologically interested in pushing the limits of synthetic data and multivariate analysis thereof, like machine learning and its generative cousins, to understand and control the errors inherent in MR data acquisitions. She is topically interested in employing these acquisitions, together with experts in non-MR methods like immunohistochemistry (IHC), ultra-high performance liquid chromatography with tandem mass spectrometry (UPLC-MS/MS), and more, to better understand, as noninvasively and equivalently as possible in both preclinical models and human patients, the multitudinous faces and fundamental mechanisms of neurodegeneration. 

Within the Glia-Immune Interactions Laboratory, Dr. Swanberg is currently driving the development of a novel MR-based method to noninvasively track potentially clinically significant cerebrospinal fluid (CSF)-mediated brain solute clearance in both mouse models and humans. She is also leading an effort to characterize the vascular, metabolic and anatomic signatures of early neurodegeneration in mouse models of Alzheimer's-like beta-amyloid aggregation, as well as to rigorously validate the potential of language-model (LM) artificial intelligence (AI) to streamline the comprehensive literature review of noninvasive magnetic-resonance research on neurofluid dynamics. 

She looks forward to further combining cutting-edge MR methods with non-MR modalities like light-sheet microscopy and flow cytometry to provide a reliable multimodal glimpse into the in vivo tissue- and postmortem cell-level manifestations of autoimmune activity in rodent models of relapse-onset multiple-sclerosis-like central nervous inflammation, as well as its potential for modulation by autologous hematopoietic stem cell (aHSC) transplantation and endogenous HSC activation. In this work, Dr. Swanberg aims to maximize the ultimate translatability of preclinical findings, in this case from experimental autoimmune encephalomyelitis (EAE) mouse models, to actually improving the lives of human individuals with multiple sclerosis.

Main Principal Investigator

• Iben Lundgaard

Co-supervisor

• David Bryder