Miroslaw Janowski, MD, PhD
Department of Diagnostic Radiology and Nuclear Medicine
Center for Advanced Imaging Research
Tumor Immunology and Immunotherapy Program
University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center
Dr. Janowski completed his residency in neurosurgery at the Medical University of Warsaw, Poland in 2009, and a year later he defended his PhD thesis in neuroscience at the Mossakowski Medical Research Centre, PAS, Warsaw, Poland. In 2011 he joined the Department of Radiology at Johns Hopkins University as a post-doctoral fellow and his career progressed to Associate Professor in 2016.
In 2019 he moved to the Department of Diagnostic Radiology and Nuclear Medicine at the University of Maryland, Baltimore. Dr Janowski’s research interests center on adding advanced imaging to accomplish precision medicine in neurointerventions. He is using radiolabeling and magnetic labeling of therapeutic agents to deliver them to the central nervous system using real-time interventional PET and MR imaging.
Select a project below to learn more.
Neonatal hypoxia-ischemia occurs in 1-3 per 1,000 full-term births, and, with approximately 4 x 106 live births in the US annually, this translates t 12,000 new patients every year with the prognosis of developmental delay. Children with developmental disabilities face challenges that hinder self-reliance, as well as educational and workplace opportunities. Stem cell therapy is a very promising strategy in regenerative medicine. There are several cell types with confirmed pre-clinical efficacy for the treatment of certain disorders, which have been approved by the FDA for clinical application. We propose to use NSI-566RSC (Neuralstem. Inc.), which are already in clinical trials for ALS and stroke, and Q-cells (Q-Therapeutics), which are in the last phase of preparation at the Johns Hopkins University for the treatment of patients with ALS. Investigating new therapeutic approaches requires disease modeling in appropriate animals. The pig is a gyrencephalic animal with a relatively large brain, and thus, is well-suited for the preclinical testing of stem cell therapies Our team established a porcine model of neonatal hypoxia/ischemia, with a detailed evaluation of behavioral and histopathological outcomes. In addition, immunodeficient rag2-/- animals are ideal recipients of human grafts. We requested the development of such pigs by the NSRRC. This request was one of only three approved in 2012, and until now the model was developed, validated and ready to use by us. The intraventricular route of cell delivery is minimally invasiv and routinely used in the clinic. We have previously shown, in a clinical case, that intraventricular deposition of iron oxide-labeled cells is safe and feasible. We have also found that the distribution of cells transplanted into the lateral ventricle of pigs is widespread, thus ideally suited for the treatment of global hypoxic/ischemic lesions, which are predominantly located in close proximity to the lateral ventricles (basal ganglia and thalamus). We have also developed a method of real-time MR monitoring of transplantation, enabling the interactive adjustment of cell delivery for outstanding precision and reproducibility. In SA1, we will test dependence of the cell distribution upon the size of cerebral ventricles and speed of intraventricular injection. Thus, in SA2, we will evaluate whether cell labeling using iron oxide nanoparticles compromises cell migration and differentiation after transplantation in a highly translational large animal model with distances traveled by the cells relevant to clinical setting. In SA3 we will perform stem cell dose finding study. In SA4, we will assess if positive therapeutic effect results from indirect mechanisms, mostly based on trophic factor release. Finally, in SA5, we will evaluate if cell replacement is feasible in large, gyrencephalic brain, an how much ii contributes to the behavioral recovery using long-term animal survival. If our study confirms therapeutic efficacy, the protocol will be ready to be applied in an early phase clinical trial, as well as provide preliminary data for cell engineering and delivery modifications for further outcome improvement.
Public Health Relevance
Neonatal hypoxia-ischemia results with life-long developmental delay, that hinder self-reliance, as well as educational and workplace opportunities. Immunodeficient rag2-/- piglets in concert with FDA-approved stem cells and minimal invasive, image-guided transplantation strategy create a unique platform to introduce regenerative medicine approach to neonatal care.
One of the many critical questions concerning stroke treatment is deciphering the ideal route of delivery in terms of efficacy, safety, timing of delivery, and methods by which to monitor the process. With an increasing number of intra-arterial catheter interventions for stroke performed, it would also seem that intra-arterial cell injection would be ideally suited in the stroke setting, as well as being quite feasible. Preclinical data suggest that intra-arterial cell injection leads to a greater number of cells targeting the ischemia. Cell sorting or cell engineering to improve the targeted delivery needs to be further investigated. The mechanistic theories about transendothelial migration and the safety concerns have led to an additional important consideration, which is the monitoring of cell delivery.
Adapted from: Guzman R, Janowski M, Walczak M. Intra-Arterial Delivery of Cell Therapies for Stroke. Stroke, 2018;49:1075–1082.
Yue Gao, MD
Jipeng Zhang, MS
Grants and Proposals
|PI||Grant Title||Total Project Period||Funding Source||Total Costs|
|Miroslaw Janowski||Image-guided, intra-arterial delivery of human mesenchymal stem cell-derived extracellular vesicles for treatment of acute ischemic stroke||06/30/19 - 06/29/21||STMD-MTDC||$533,025.00|
Total Cost: $533,025.00
Click here to view Dr. Janowski's publications on PubMed.