Using Dental Pulp Stem Cells for Stroke Therapy

I still prefer handing your doctor a pee cup and asking for stem cells in return. 

Turning urine into brain cells could help fight Alzheimer’s, Parkinson’s

December 2012

 

Did this from August 2016 provide any answers?  Did you even know about it? 

TOOTH (The Open study Of dental pulp stem cell Therapy in Humans): Study protocol for evaluating safety and feasibility of autologous human adult dental pulp stem cell therapy in patients with chronic disability after stroke

The latest here:

Using Dental Pulp Stem Cells for Stroke Therapy

Maria R. Gancheva^1*, Karlea L. Kremer¹, Stan Gronthos^2,3 and Simon A. Koblar^1,3,4

• ¹Stroke Research Programme Laboratory, Adelaide Medical School, Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, SA, Australia
•  ³South Australian Health and Medical Research Institute, Adelaide, SA, Australia
• ⁴Central Adelaide Local Health Network, Adelaide, SA, Australia

Stroke is a leading cause of permanent disability world-wide, but aside from rehabilitation, there is currently no clinically-proven pharmaceutical or biological agent to improve neurological disability. Cell-based therapies using stem cells, such as dental pulp stem cells, are a promising alternative for treatment of neurological diseases, including stroke. The ischaemic environment in stroke affects multiple cell populations, thus stem cells, which act through cellular and molecular mechanisms, are promising candidates. The most common stem cell population studied in the neurological setting has been mesenchymal stem cells due to their accessibility. However, it is believed that neural stem cells, the resident stem cell of the adult brain, would be most appropriate for brain repair. Using reprogramming strategies, alternative sources of neural stem and progenitor cells have been explored. We postulate that a cell of closer origin to the neural lineage would be a promising candidate for reprogramming and modification towards a neural stem or progenitor cell. One such candidate population is dental pulp stem cells, which reside in the root canal of teeth. This review will focus on the neural potential of dental pulp stem cells and their investigations in the stroke setting to date, and include an overview on the use of different sources of neural stem cells in preclinical studies and clinical trials of stroke.

Introduction

The central nervous system (CNS) functions through complex molecular and cellular interactions, and disruption by severe injury or disease leads to irreversible neuronal loss and associated functional deficits. This results in highly debilitating pathologies associated with significant health and economic burden for patients, their families, carers, and the health systems.

Stroke is a global health care problem and a leading cause of acquired adult neurological disability (1). With an aging population, the incidence and prevalence of stroke is predicted to rise. A stroke is characterised by reduced and insufficient blood supply to part of the brain. Inadequate oxygen and nutrients lead to tissue infarction, resulting in disability due to loss-of-function associated with the damaged area of the brain.

There are two main types of stroke; haemorrhagic and ischaemic. Haemorrhagic strokes, accounting for 13 percent of strokes (1), result from bleeding when a blood vessel is ruptured. Ischaemic stroke is the most common presentation of stroke at 87 percent of all cases (1), and is due to an obstruction in the blood supply, which could be formed locally (thrombosis) or formed elsewhere in the body (embolism).

During an ischaemic stroke, a complex chain of events takes place at the molecular and cellular levels, which results in cell necrosis at the site of the vascular insult (the ischaemic core), while the region surrounding the core (the ischaemic penumbra) remains viable for some time due to collateral blood supply and can thus be salvaged. A strong inflammatory response is initiated within hours of stroke onset, characterised by reactive astrogliosis, microglial activation, disruption to the blood-brain barrier (BBB), and infiltration of neutrophils and monocytes/macrophages (2). Growth factors and inflammatory mediators, from local glial and inflammatory cells, alter the reaction of endogenous neural stem and progenitor cells. Over time, reorganisation of the neural network around the core takes place. If untreated, the penumbra will transform into ischaemic tissue, expanding the irreversibly damaged area of brain. There is an opportunity to save the penumbral tissue via acute recanalisation therapies.

The currently available therapeutic interventions, such as thrombectomy and thrombolysis, are limited to a narrow therapeutic window and eligibility criteria, and though they have a significant impact on stroke outcome, disability remains after any intervention. Thrombectomy refers to the mechanical removal of a blood clot, which has been effective when performed within 24 h post-stroke (3). The more common intervention is thrombolysis by intravenously administered recombinant tissue plasminogen activator, to breakdown the clot. This is currently the only approved pharmacological agent that shows significant benefits in acute ischaemic stroke, but is only applicable within a short time frame of 4.5 h from symptomatic onset (4). Unfortunately, many patients are ineligible for these reperfusion therapies. In addition, poor patient outcomes can still be observed. Once a stroke patient is stabilised, rehabilitation interventions are relied upon to promote neuroplasticity, as patients adapt to residual disability. Improvements are most significant in the first several months following a stroke (5). There is currently no therapy that can restore damaged neural tissue and its associated functions.

Cell-based therapies have the potential to promote functional recovery in patients affected by stroke and other neurological diseases. Stem cells are promising candidates, as they can act through multiple cellular and molecular mechanisms to provide support for endogenous cells, stimulate endogenous processes, and act as a source of cell replacement. Neural stem cells (NSC), which reside in specific areas of the CNS, are the most appropriate stem cells for brain repair. Research is focused on two therapeutic paradigms; enhancing and manipulating endogenous NSC, and implanting exogenous NSC. Reprogramming strategies are being applied to develop NSC from more easily accessible and abundant cell types (6). Dental pulp stem cells (DPSC) are adult stem cells obtained from the dental pulp tissue in the tooth chamber (7). These cells are easily sourced and have neurogenic potential. They are being investigated as an alternative source of neural cells and in preclinical models of neurological diseases, including stroke. This review will focus on the potential use of human DPSC for stroke therapy and will include an overview of different types of NSC being studied.