Potential Therapeutic Approaches for Stroke Using Induced Pluripotent Stem Cells

Review Article

Austin J Biomed Eng. 2014;1(4): 1016.

Potential Therapeutic Approaches for Stroke Using Induced Pluripotent Stem Cells

Valerio LSA1,2 and Sugaya K3*

1Institute for Scientific Research and Technology Services (INDICASAT), City of Knowledge, Republic of Panama.

2Department of Biotechnology, Acharya Nagarjuna University, Guntur, India

3Burnett School of Biomedical Sciences, University of Central Florida, USA.

*Corresponding author: :Sugaya K, Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, 6900 Lake Nona Boulevard, Orlando, FL, 32827, USA.

Received: July 02, 2014; Accepted: July 31, 2014; Published: Aug 01, 2014


Stroke is a principal cause of mortality in most countries and up to date there is no cure or potential therapeutic treatment available for this debilitating condition. Human induced pluripotent stem (hiPS) cells are an important source for autologous cells used in regenerative medicine in order to treat brain damage after a stroke has occurred. Recent studies have suggested that transplanted neural cells derived from hiPS cells have the potential to survive, differentiate and improve motor behavior in stroke animal models. In this review, we discuss the conditions needed to reprogram hiPS cells for clinical trials, the strategies used to differentiate hiPS cells toward neural stem cells (NSC) lineage along with their functionality and morphological characteristics studied in vitro. We further address the features founded in vivo after graft transplantation of these neural cells into stroke animal models.

Keywords: Stroke; Stem Cells; Transplantation; Neural tissue


hiPS: Human induced pluripotent stem cells; NSC: Neural Stem Cells


Stroke is a leading cause of mortality and disability worldwide. About 750,000 people experience a modality of strokes each year, and the cost of maintaining these patients’ reaches in excess of billions just in USA [1]. Stroke is a condition in which the brain of an individual is deprived of oxygen and nutrients because the lack of blood supply, which results in death or loss of neural functions. This event is generated by the rupture of an artery/blood vessel in the hemorrhagic stroke, or by the obstruction of a blood vessel for a clot in the ischemic stroke.

The consequences of the damage depend primarily on the area affected, the magnitude of the lesion, the immune response (which may increase damage due to the release of reactive oxygen species and chemokines that attack healthy neurons) and neurorepair mechanisms. If the patients are affected in their locomotor and/or sensory motor areas, then these patients may experience the loss of well-coordinated movements, speech, remembrance, feeling or even total disability. Occipital lobe lesions may disrupt the ability to see; temporal lobe lesion may affect the ability to hear; parietal lobe lesion may interrupt sensory information; and frontal lobe may affect cognition.

Stroke is a sudden and delayed death disease. It is not clear whether a specific genetic mutation or a combination of mutations are directly responsible for the attack, but a study in twins suggests that genetics may be involved in the development of the disease [2]. Interestingly enough, it has been associated with several genes (i.e., the NINJ2 gene, located in chromosome 12p13) as a high-risk biomarker factors to develop hemorrhagic and ischemic stroke [3]. The risk of developing cerebrovascular disease increases in patients with aneurism (which actually is a direct cause of loss of blood supply), hypertension, obesity, high levels of cholesterol in the blood and smoking [1].

A possible treatment of ischemic stroke is recanalization, with the aim to lysate the clots by surgical intervention. An alternative method to lyse the clots is the tissue Plasminogen Activator (tPA) [4], which is the only accepted drug used to treat this disease in clinics at the present. However, this approach has been limited for few patients under specific conditions as the magnitude of the insult (small areas affected), the time since the ictus has occurred (less than 3 hours) and the age of the patient [5]. In contrast, the hemorrhagic stroke has no drugs available to recover the blood supply lost or to improve behavior in patients, and tPA is contraindicated. Importantly, it is known that patients themselves have improved recovery on their own after stroke, probably due to the combination of recovery mechanisms related to neurogenesis.

The application of stem cells in regenerative medicine for stroke has demonstrated to improve recovery after the insult by neurorepair mechanism. However, the use of embryonic stem (ES) cells and adult stem cells (i.e., neural stem cells, mesenchymal stem cells, among others) has different limitations. First, the methods to obtain the samples, involve the death of embryos (in the case of ES cells) or the extraction may be painful and difficult for patients (i.e., adult stem cells from bone marrow). Second, depending on the adult stem cell source, it may be difficult to differentiate the somatic cells of interest. Third, in cases of allogeneic transplantation, autoimmune rejection can occur afterwards because stem cells will have different patterns of molecules from the patient who will receive the graft. Finally, all the limitations together give rise to discrepancies in the ethical concern for uses in clinics and research [6].

hiPS cells prepared for clinical trials

Somatic cells can be reprogrammed to an induced pluripotent stem (iPS) cells by activating pluripotent-signaling pathways shown in Figure 1 [7,8]. These novel kinds of cells with the potency similar to ES cells, avoid the possibility of cell rejection by the host because they are derived from the patient’s own cells (autologous). The major goal of this approach is to ensure an easy source of pluripotent cells, which have the ability to produce somatic cells, including neuroectodermal progenitors without incurring in ethical issues. Thus, iPS cells are a better choice to use in clinical trials compared to their counterpart ES cells for a pluripotent cell source.