You are here

| Mesenchymal Stem Cells

The hMSC Secretome: An Effective Cell-free Therapy for Parkinson’s Disease?

Comment

Discuss

Review of “Impact of the Secretome of Human Mesenchymal Stem Cells on Brain Structure and Animal Behavior in a Rat Model of Parkinson’s Disease” from Stem Cells Translational Medicine by Stuart P. Atkinson

While transdifferentiation and cell fusion remain as potential mechanisms behind the success of human mesenchymal stem cell (hMSC)-based therapeutics, the paracrine action of hMSC-secreted factors remains as the most likely candidate. A recent Stem Cells Translational Medicine study from the lab of António J. Salgado (University of Minho, Braga, Portugal) sought to assess the potential of the hMSC “secretome” as a potential treatment for the Parkinson’s disease (PD) given previous studies indicating neuroprotective/neurostimulatory activity [1-3]. 

For this purpose, Teixeira et al assessed dopaminergic (DA) neuron survival and motor function following hMSC secretome injection into the substantia nigra and striatum of a 6-hydroxidopamine (6-OHDA) Parkinson’s disease (PD) rat model [4]. Could this represent the beginnings of an effective cell-free therapy for PD?

To first collect secretome samples to inject into the PD model, the authors turned to computer-controlled suspension bioreactor technology for hMSC culture. This system permits the collection of potentiated conditioned growth medium highly enriched with pro-neuroregulatory factors secreted from hMSCs [5].

As expected, 6-OHDA injections led to notable impairments in animal behavior, motor performance, and motor coordination; however, the injection of hMSC secretome attenuated these deficits. Histological analysis of rat brains demonstrated that hMSC secretome injection promoted the survival of tyrosine hydroxylase (TH)-positive DA neurons in both the substantia nigra and the striatum. Non-targeted and targeted proteomic analysis of the secretome correlated secretome-induced improvements with the presence of known neurotrophic factors (such as VEGF, BDNF, IL-6, and GDNF) and also novel, potentially interesting proteins such as Cys C, GDN, Gal-1, and PEDF.

Overall, this paper suggests that the bioreactor-potentiated hMSC secretome contains important neuroregulatory factors that could form part of an effective cell-free therapy for PD. Moving forward; the authors hope to fine-tune the hMSC secretome-creation process in order to capture the full power of the secretome and to delineate the intertwined roles of the neuroregulatory factors identified.

References

  1. Jin GZ, Cho SJ, Lee YS, et al. Intrastriatal grafts of mesenchymal stem cells in adult intact rats can elevate tyrosine hydroxylase expression and dopamine levels. Cell Biol Int 2009;34:135-140.
  2. McCoy MK, Martinez TN, Ruhn KA, et al. Autologous transplants of Adipose-Derived Adult Stromal (ADAS) cells afford dopaminergic neuroprotection in a model of Parkinson's disease. Exp Neurol 2008;210:14-29.
  3. Fu YS, Cheng YC, Lin MY, et al. Conversion of human umbilical cord mesenchymal stem cells in Wharton's jelly to dopaminergic neurons in vitro: potential therapeutic application for Parkinsonism. Stem Cells 2006;24:115-124.
  4. Teixeira FG, Carvalho MM, Panchalingam KM, et al. Impact of the Secretome of Human Mesenchymal Stem Cells on Brain Structure and Animal Behavior in a Rat Model of Parkinson's Disease. STEM CELLS Translational Medicine 2017;6:634-646.
  5. Teixeira FG, Panchalingam KM, Anjo SI, et al. Do hypoxia/normoxia culturing conditions change the neuroregulatory profile of Wharton Jelly mesenchymal stem cell secretome? Stem Cell Res Ther 2015;6:133.