Intrinsic Angiogenic Potential and Migration Capacity of Human Mesenchymal Stromal Cells Derived from Menstrual Blood and Bone Marrow.

Rosana De Almeida Santos,Tais Hanae Kasai-Brunswick,Ingrid Rosenburg Cordeiro,Karina Dutra Asensi,José Marques De Brito Neto,Rafael Campos Silva De Menezes,Julia Helena Oliveira De Barros,Regina Coeli Dos Santos Goldenberg

doi:10.3390/ijms21249563

Abstract

Several therapies are being developed to increase blood circulation in ischemic tissues. Despite bone marrow-derived mesenchymal stromal cells (bmMSC) are still the most studied, an interesting and less invasive MSC source is the menstrual blood, which has shown great angiogenic capabilities. Therefore, the aim of this study was to evaluate the angiogenic properties of menstrual blood-derived mesenchymal stromal cells (mbMSC) in vitro and in vivo and compared to bmMSC. MSC’s intrinsic angiogenic capacity was assessed by sprouting and migration assays. mbMSC presented higher invasion and longer sprouts in 3D culture. Additionally, both MSC-spheroids showed cells expressing CD31. mbMSC and bmMSC were able to migrate after scratch wound in vitro, nonetheless, only mbMSC demonstrated ability to engraft in the chick embryo, migrating to perivascular, perineural, and chondrogenic regions. In order to study the paracrine effects, mbMSC and bmMSC conditioned mediums were capable of stimulating HUVEC’s tube-like formation and migration. Both cells expressed VEGF-A and FGF2. Meanwhile, PDGF-B was expressed exclusively in mbMSC. Our results indicated that mbMSC and bmMSC presented a promising angiogenic potential. However, mbMSC seems to have additional advantages since it can be obtained by non-invasive procedure and expresses PDGF-B, an important molecule for vascular formation and remodeling.

Highlights

Over the past few decades, ischemic diseases are the most common causes of deaths in the world
Our results showed that only menstrual blood-derived mesenchymal stromal cells (mbMSC) were able to survive in the chick embryonic microenvironment, as well as being able to integrate into host tissues, participating in morphogenesis along with embryo cells. mbMSC presented a tropism for presumptive chondrogenic regions of the chick embryo, since 8.3% of these cells were found in territories close to the notochord
MbMSC and bone marrow-derived mesenchymal stromal cells (bmMSC) were able to migrate after scratch wound in vitro, only mbMSC demonstrated the ability to migrate and integrate into host tissues in vivo, responding in a particular way to different embryonic signals, being able to engraft in perivascular, perineural and chondrogenic regions

Summary

Introduction

Over the past few decades, ischemic diseases are the most common causes of deaths in the world. Of this group, ischemic heart disease and stroke are the ones that require great attention [1], currently responsible for approximately 15 million deaths in 2019 [2], and critical limb ischemia, a serious form of peripheral artery disease, represents the third most prevalent form of atherosclerotic cardiovascular disease [3]. The idea of promoting increased blood perfusion in ischemic tissues via angiogenesis may be promising. Considering that ischemic disorders can be primarily caused by endothelial dysfunction, the logic behind therapeutic angiogenesis would be related to the promotion of vascular repair via endothelial cells and/or administration of growth factors [4,5,6,7]. The regenerative potential of MSC is so promising that several groups are already developing delivery methods of MSC on a 3D cell-delivery platform, which can be an alternative to improve cryoprotection, graft survival, angiogenic activity and prolonged cell function in vivo in order to explore the full potential of MSC in regenerative medicine [26]

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