Objective: This is a systematic review of the effects of low-intensity pulsed ultrasound
(LIPUS) on stem cell differentiation.
Background Data: Recent studies have investigated several types of stem cells from different sources
in the body. These stem cells should strictly be certified and promoted for cell therapies before being
used in medical applications. LIPUS has been used extensively in treatment centers and in research to
promote stem cell differentiation, function, and proliferation.
Materials and Methods: The databases of PubMed, Google Scholar, and Scopus were searched for
abstracts and full-text scientific papers published from 1989-2019 that reported the application of
LIPUS on stem cell differentiation. Related English language articles were found using the following
defined keywords: low-intensity pulsed ultrasound, stem cell, differentiation. Criteria for inclusion in
the review were: LIPUS with frequencies of 1–3 MHz and pulsed ultrasound intensity of <500
mW/cm2. Duration, exposure time, and cell sources were taken into consideration.
Results: Fifty-two articles were selected based on the inclusion criteria. Most articles demonstrated that
the application of LIPUS had positive effects on stem cell differentiation. However, some authors recommended
that LIPUS combined with other physical therapy aides was more effective in stem cell
Conclusion: LIPUS significantly increases the level of stem cell differentiation in cells derived mainly
from bone marrow mesenchymal stem cells. There is a need for further studies to analyze the effect of
LIPUS on cells derived from other sources, particularly adipose tissue-derived mesenchymal stem cells,
for treating hard diseases, such as osteoporosis and diabetic foot ulcer. Due to a lack of reporting on standard
LIPUS parameters in the field, more experiments comparing the protocols for standardization of
LIPUS parameters are needed to establish the best protocol, which would allow for the best results.