Therapeutic potential of mesenchymal stem cells for cerebral small vessel disease

Abstract

Cerebral small vessel disease (CSVD), as the most common, chronic and progressive vascular disease on the brain, is a serious neurological disease, whose pathogenesis remains unclear. The disease is a leading cause of stroke and vascular cognitive impairment and dementia, and contributes to about 20% of strokes, including 25% of ischemic strokes and 45% of dementias. Undoubtedly, the high incidence and poor prognosis of CSVD have brought a heavy economic and medical burden to society. The present treatment of CSVD focuses on the management of vascular risk factors. Although vascular risk factors may be important causes or accelerators of CSVD and should always be treated in accordance with best clinical practice, controlling risk factors alone could not curb the progression of CSVD brain injury. Therefore, developing safer and more effective treatment strategies for CSVD is urgently needed. Recently, mesenchymal stem cells (MSCs) therapy has become an emerging therapeutic modality for the treatment of central nervous system disease, given their paracrine properties and immunoregulatory. Herein, we discussed the therapeutic potential of MSCs for CSVD, aiming to enable clinicians and researchers to understand of recent progress and future directions in the field.

Keywords: Cell therapy; Cerebral small vessel disease; Mesenchymal stem cell; Neurological disorders.

Fig. 1

CSVD overview. BBB: Blood-brain barrier; BCSFB: Blood-cerebrospinal fluid barrier; CSVD: Cerebral small vessel disease; EC: Endothelial cell; WMH: White matter hyperintensity; SMC: Smooth muscle cell.

Fig. 2

The possible therapeutic mechanism of MSCs in CSVD. MSC treatment can modulate different cellular components of the neurovascular unit, regulate the neurotransmitter system and reduce abnormal production. ACh: Acetylcholine; AChE: Acetylcholinesterase; AChR: Acetylcholine receptor; AQP4: Aquaporin-4; Aβ: Amyloid beta; ChAT: Choline acetyltransferase; GABA: gamma-aminobutyric acid; GABABR1: gamma-aminobutyric acid-B receptor 1; GAD67: glutamic acid decarboxylase 67; IL-1β: interleukin-1β; IL-10: interleukin-10; IFN-γ: interferon gamma; MMP-2: matrix metalloproteinase-2; TGF-β: transforming growth factor-beta.