You are here

| Muscle Stem Cells

Magnetic Sorting Promotes Clinical Applicability of Smooth Muscle Progenitor Cells

Comment

Discuss

Review of “Efficacy and Safety of Immuno-Magnetically Sorted Smooth Muscle Progenitor Cells Derived from Human-Induced Pluripotent Stem Cells for Restoring Urethral Sphincter” from STEM CELLS Translational Medicine by Stuart P. Atkinson

In both men and women, urethral sphincter muscle injury or atrophy can lead to the development of stress urinary incontinence (SUI). Smooth muscle progenitor cells (pSMCs) differentiated from human induced pluripotent stem cells (hiPSCs) [1, 2] can restore the structure and function of urethral sphincter in an SUI animal model [3, 4]; however, the current protocol requires the clinically unapproved fluorescence-activated cell sorting (FACS) technique.

To solve this sorting problem, researchers from the laboratory of Yan Wen (Stanford University School of Medicine, California, USA) assessed whether a clinically approved magnetic-activated cell sorting (MACS) technique [5] may substitute for FACS and promote the clinical application of hiPSC-derived smooth muscle progenitor cells for SUI [6].

The authors compared vascular progenitor cells (VPCs) differentiated from hiPSCs after sorting via MACS or FACS using CD31 and CD34 antibodies. While FACS provided better purity compared to MACs (~96% vs. ~60-70%), the presence of undifferentiated hiPSCs significantly decreased in both cultures after smooth muscle cell-directed differentiation of VPCs in vitro. Indeed, pSMC-like spindle-shaped cells appeared after 14 days of culture and all cells began to express important myogenic proteins (SMA and SM-22).

Encouragingly, the smooth muscle progenitor cells generated from MACS-sorted VPCs did not form tumors in immunodeficient mice following periurethral injection in SUI model rats (See Figure), but smooth muscle progenitor cells did increase elastin expression in the damaged urethral sphincter and induced functional repair to a level similar to cells derived from FACS sorted VPCs.

The MACs vs. FACS showdown indicates that magnetic sorting has the potential to promote the clinical applicability of hiPSC-derived smooth muscle progenitor cells for the treatment of SUI. Safe, cheap, and clinically approved; what other degenerative smooth muscle conditions can MACS sorted pSMCs help to treat?

Stay tuned to the Stem Cells Portal to find out!

References

  1. Marchand M, Anderson EK, Phadnis SM, et al. Concurrent generation of functional smooth muscle and endothelial cells via a vascular progenitor. Stem Cells Transl Med 2014;3:91-97.
  2. Lian X, Bao X, Al-Ahmad A, et al. Efficient differentiation of human pluripotent stem cells to endothelial progenitors via small-molecule activation of WNT signaling. Stem Cell Reports 2014;3:804-816.
  3. Wang Z, Wen Y, Li YH, et al. Smooth Muscle Precursor Cells Derived from Human Pluripotent Stem Cells for Treatment of Stress Urinary Incontinence. Stem Cells Dev 2016;25:453-461.
  4. Li Y, Wen Y, Wang Z, et al. Smooth Muscle Progenitor Cells Derived From Human Pluripotent Stem Cells Induce Histologic Changes in Injured Urethral Sphincter. Stem Cells Transl Med 2016;5:1719-1729.
  5. Barral S, Ecklebe J, Tomiuk S, et al. Efficient neuronal in vitro and in vivo differentiation after immunomagnetic purification of mESC derived neuronal precursors. Stem Cell Res 2013;10:133-146.
  6. Li Y, Green M, Wen Y, et al. Efficacy and Safety of Immuno-Magnetically Sorted Smooth Muscle Progenitor Cells Derived from Human-Induced Pluripotent Stem Cells for Restoring Urethral Sphincter Function. STEM CELLS Translational Medicine 2017;6:1158-1167.