Problems to be Solved by h.o.p.e.

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The central nervous system is made up of thousands of cell types. The major categories are neurons, astrocytes, oligodendrocytes, glial scar, pericytes, vasculature, lymphatics, ependymal, cerebrospinal system, extracellular matrix, and microglia. They all play an important role in a normal functioning brain. The absence of each and any cell type results in a known pathological disorder. Deciding to replace or treat only one cell type essentially overlaps a known pathologic condition onto the existing neurologic injury. Therefore, all must be replaced in order to restore function after a neurological injury. However, no industry or academic lab has undertaken a fully comprehensive cell biology approach to repair.

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A new comprehensive biology team is necessary for a successful approach to tissue regrowth.

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Technology to be Orchestrated 

Comprehensive Cell Biology

The central nervous system is made of thousands of cell types. The major categories are the following: 

1. Neurons: process and transmit information that underpin all functions;

2. Astrocytes: blood brain barrier, process information, glial scar formation, process metabolites;

3.  Oligodendrocytes: increase conduction speed of information;

4. Glial scar: limits damage from spreading, barrier to new growth, influences immune system; 

5. Pericytes: integral to blood supply and tissue remodeling;

6. Vasculature: supplies metabolites, stem cell migration pathway;

7. Lymphatic: clears extracellular fluid;

8. Ependymal: forms the cerebrospinal system compartments;

9. Cerebrospinal system and choroid plexus: cools the brain, establishes growth factor gradients;

10. Extracellular matrix: provides tertiary structure for brain, component of scar tissue;

11. Microglia: immune cells of brain, regulates new synapse formation.

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Human physiology is now better understood than ever before. We understand only a minority of cells are neurons, and they are actually part of a complex unit of different cell types. We understand the enormous influence that blood vessels exert in the brain, the cerebrospinal system’s ability to shape the structure of the brain, the effect of 3D growth on cell morphology, the effect of flowing hydrodynamic mechanical forces on cell function and form, and the other thousands of parts integrated into the trillion-cell supercomputer which is our central nervous system. 

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It is a generational achievement that this level of cellular biology information is available in multiple databases such as PubMed (the national literature database supported by the National Institute of Health). Searching for the scientific literature on pro-growth strategies alone (cell types, growth factors, metabolism, apoptosis, cell adhesion, guidance cues, cell migration, nutrient migration, network integration – local, regional, distant, etc.) yields over 12 million papers. This level of complexity needs to be organized into translational steps, and no part ignored.

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Every field of neuroscience will be greatly improved by adding a comprehensive biologic approach and a bold insistence to solve the problem of regrowing a single patient’s missing neurological tissue. This applies to knowledge bases, imaging, understanding neurological injury, improving computer models of repair, designing therapeutic repair strategies, and conducting laboratory cell culture experiments. This is the paradigm shift that will permanently shape the field of personalized neurorepair and begin to close the translational gap between this enormous scientific expertise and individual patient treatment plans. 

 

Goal of h.o.p.e.

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Cell biologists spend decades developing sophisticated vertical and horizontal knowledge about their one cell of expertise. They have strong opinions on what the best papers are, the best growth factors, the best cell sources, etc. For each of these decision points, the specific scientific talent will be assembled to orchestrate the best practices available to date. This is the vehicle by which each scientific soloist can imagine, decide, and implement exactly what is needed to regrow their part of a specific patient’s missing tissue.

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Artificial Intelligence Pro-Growth Knowledge Base 

Comprehensive cell biologists will work with the bioinformatics and artificial intelligence teams to curate the literature base by each cell type to improve all decision points regarding tissue regrowth.

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Missing Tissue Hologram

Comprehensive cell biologists will calculate 1) the total amount of the patient’s glial scar tissue; 2) the number of missing neurons, astrocytes, oligodendrocytes, pericytes, vasculature, lymphatics, ependymal, cerebrospinal system, extracellular matrix, and microglia resulting from the patient’s injury; and 3) the extent of the patient’s missing neurons, astrocytes, oligodendrocytes, pericytes, vasculature, lymphatics, ependymal, cerebrospinal system, extracellular matrix, and microglia 
cellular networks.

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Regrowth Simulation 

Comprehensive cell biologists will calculate what is needed to 1) remove all the patient’s glial scar tissue; 2) replace all the patient’s missing cells; and 3) reconnect all the patient’s missing cellular networks.

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Comprehensive Cell Biology

Comprehensive cell biologists will calculate what is needed to 1) keep the injury cavity permeable; 2) ensure the survival and function of each cell type regarding their absolute requirements of growth factors, metabolites, blood supply, cell trafficking, cell communication, apoptosis, cell adhesion, cell-cell interactions, guidance cues, gap junctions, etc.; and 3) ensure the survival and function of each cellular network regarding the absolute requirements of growth factors, metabolism, apoptosis, cell adhesion, guidance cues, cell migration, nutrient migration, network integration – local, regional, and distant, gap junctions, synapses, etc.  

 

Regrowth Regimen 

Comprehensive cell biologists will decide 1) what is the best cell replacement source per cell type; 2) which drugs, dose, duration, sequence, delivery, toxicity, and excretion are needed to remove the glial scar; 3) which drugs, dose, duration, sequence, delivery, toxicity, and excretion are needed for each cell type survival and function; and 4) which drugs, dose, duration, sequence, delivery, toxicity, and excretion are needed for each cellular network survival and functional integration.

 

Lab Clinical Trial

Comprehensive cell biologists and physicians will decide what is required for 1) drug delivery in a clinically simulated lab trial to regrow the patient’s missing tissue; 2) clinical protocol orchestration and rehearsal; and 3) Food and Drug Administration and Hospital Institutional Review Board applications. 

 

Impact of h.o.p.e. 

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No academic or industry lab has a commitment to a comprehensive cell biology approach given the scale, scope, complexity, and current career incentives, thereby resulting in the oversimplification of treatment strategies. These diverse cell types in the central nervous system are irrefutable facts of nature. Ignoring them may be more expedient and simple, but this guarantees translational failure, as evidenced by the tens of thousands of failed clinical trials. With this new commitment to comprehensive cell biology, the field of neuroscience will have a new standard to be met, and, finally, enhanced rigorous calculations will be applied on the human scale to an individual. For the first time, a single injury will have a repair strategy built around a complete understanding of all of the involved cells, the length of the missing cellular networks, and the individual requirements for the functioning of each cell.