Exosomes Paracrine Signaling
• Paracrine signaling is a form of cell-to-cell communica2on where a
cell produces a signal to induce changes in nearby cells, altering the
behavior of those cells.
• Paracrine factors diﬀuse over a rela2vely short distance, as opposed
to hormones which can travel long distances
• It has been studied that exosomes can travel long distances and even
cross the blood brain barrier
TARGET TISSUES :
On studies demonstrate that PRP derived exosomes recapitulate the broad therapeu;c
eﬀects previously a>ributed to HSCs/MSCs/T-cells/B-Cells via horizontal transfer of mRNAs,
miRNAs, and proteins
How could patients benefit from Exosomes?
• iExosomes and their potential benefits in the regenerative
medicine therapies :
• Orthopedics : Joints, Muscles, Bones, Discs, Ligaments , Tendons
• Wound Care
• Hair loss
• Heart Disease
• Liver Disease
• Lung Disease : COPD, Inters22al Lund Disease
• Kidney Disease
• Neurodegenera2ve disorders : Mul2ple Sclerosis, Alzheimers, Parkinsons, Spinal cord Injuries
• Auto-immune Diseases
• And more!
• One study demonstrated that micro-vesicles from endothelial progenitor cells ﬁght kidney damage from
ischemic events by packaging miRNA responsible for ac2va2ng regenera2ve programs in the kidney
Studies showing PRP Exosome
• Human umbilical cord Blood Plasma MSC/HSC derived exosomes help
in facilita2ng healing pathways in burn models
• Wounds treated with exosomes exhibited accelerated reepitheliza2on and
increased expression of CK19, PCNA, and collagen I
• Exosomes promote collagen synthesis and angiogenesis
(development of new blood vessels)
• PRP derived exosomes increased prolifera2on and migra2on of
ﬁbroblasts in order to enhance wound healing.
• PRP derived exosomes recapitulate the broad therapeu2c
eﬀects previously a[ributed to HSCs/MSCs/T-cells/B-Cells via
horizontal transfer of mRNAs, miRNAs, and proteins
What Types of Medical Conditions Might Be aided by PRP
• Cerebral Palsy, Au;sm
• Neuropathy, CIDP
• Erec;le Dysfunc;on
• Urinary Incon;nence
• Complex Regional Pain Syndrome
• Chronic Pelvic Pain
• Lyme Disease (Upregulate Macrophages)
• Numerous Aesthe;c Applica;ons
What are the advantages of iEXOSOMES
• Acellular Product ( No live cells )
• Can be used in local and systemic therapy
• Ability to cross the Blood-Brain-Barrier (BBB)
• Cannot diﬀeren2ate into diﬀerent cells
• Potency related to parent cell (HSC, MSC, , ESC, WBC, etc)
• Easy controlled dosage
• Easy to administer, store, and freeze
• No chance of gene2c muta2ons or Cancer-linked muta2on
• No risk of clumping
• Fresh source-No risk of culturing and contamina2on
• No risk of Gra^ Versus Host disease ( GVHD)
The importance of Cell signaling :
• Mul2potent MSCs reside in speciﬁc 2ssue niches composed of cells crea2ng
speciﬁc microenvironment for 2ssue-resident progenitor cells and facilitate them
to maintain 2ssue homeostasis.
• Niche cells provide signals which regulate and control the balance of self-renewal
and diﬀeren2a2on capacity of stem/progenitor cells residing in them.
• The niche also controls stem/progenitor cell division and ac2vity to preserve
cancer forma2on. The balance of progenitor cell quiescence and ac2vity is a
hallmark of a func2onal niche and is regulated by internal (e.g., DNA damage)
and external signals leading to self-renewal and diﬀeren2a2on of progenitor
It has been shown that exosomes contain large amounts of miRNAs and can serve as vehicles to transfer
miRNAs to recipient cells, where the exogenous miRNAs can alter the gene expression and bioac2vity of
• Our results show that iEXOSOMES can eﬀec2vely enhance cutaneous wound healing in mice and the
underlying mechanism may be their ac2va2on of func2on proper2es of ﬁbroblasts and endothelial cells
in the wounds, as iEXOSOMES can enhance the prolifera2on and migra2on of ﬁbroblasts, as well as the
angiogenic ac2vi2es of endothelial cells in vitro
In the regula2on of ﬁbroblast func2on and endothelial angiogenesis, miR-21-3p
plays a crucial role since suppression of miR-21-3p can markedly reduce the regulatory eﬀects of exosomes
• Our ﬁndings suggest that iEXOSOMES may represent a novel therapeu;c tool for soU ;ssue wound
• Chronic wounds have become an economic, social, and public health burden and need advanced
treatment. Platelet-rich plasma (PRP) has been used extensively in treatment of chronic wounds
because it contains an abundance of growth factors secreted by platelets.
• The exosomes derived from PRP (PRP-Exos) have been proven to encapsulate principal growth factors
• Preliminary analysis of exosome content showed that PRP-Exos encapsulated bFGF, PDGF-BB, VEGF,
and TFG-β. Our ﬁndings indicate that exosomes released by PRP may contribute to PRP-induced
angiogenesis through ac2va2on of Erk and Akt signaling pathways, and suggest that PRP-induced re-
epithelializa2on may be triggered by ac2va2on of YAP .
• The regenera2ve poten2al of exosomes may be modulated or tuned by prior exposure of the origina2ng cell
popula2on to external s2muli. For example, inﬂammatory condi2oning of human umbilical cord blood
derived MSCs with IFN-γ (interferon-γ) to protect against acute ischemic renal injury in vivo .
• Umbilical Cord blood is a great source of CD 34+; as the result , -PRP contains great amount of Exosomes
secreted from CD 34+ cells.
Neurological disorders :
• The derived exosomes took part in the regula2on of endothelial cell func2ons, possessed
direc2on through which to study epigene2c phenomena and congenital diseases.
pro- angiogenic characteris2cs, which was at least par2ally a[ributable to the miRNAs contained
• Although intrauterine angiogenesis is regulated by various factors, exosomal miRNAs may play
• Our study developed a novel explana2on for the development of IUGR, as well as a new
signiﬁcant regula2on roles in this important process.
• Their simple structure and ability to cross the blood-brain barrier allow great opportunity to design a “makeup” with drugs
and gene2c elements, such as siRNA or miRNA, and use them as delivery vehicles for neurotherapeu2cs
Injec2on of exosomes into injured mouse hearts recapitulates the regenera2ve and func2onal eﬀects produced by CDC
transplanta2on, whereas inhibi2on of exosome produc2on by CDCs blocks those beneﬁts.
• CDC exosomes contain a dis2nc2ve complement of microRNAs, with par2cular enrichment of miR-146a.
• Selec2ve administra2on of a miR-146a mimic reproduces some (but not all) of the beneﬁts of CDC exosomes.
The ﬁndings iden2fy exosomes as key mediators of CDC-induced regenera2on, while highligh2ng the poten2al u2lity of
exosomes as cell-free therapeu2c candidates.
Orthopedic/Joint diseases :
Joint diseases have a wide range and can inﬂuence the car2lage, subchondral bone, and synovium, destroying
• Exosomes, which are important for communica2on among cells, are involved in joint diseases.
• Exosomes in synovial ﬂuid or released from synovial ﬁbroblasts could induce joint disease progression.
• Exosomes in blood could be helpful in diagnosing joint diseases.
• Exosomes from stem cells could delay diseases and repair joints. The emerging role of exosomes will improve the
development of mechanisms, diagnoses and therapeu2c research.
Hair loss :
• Hair follicles are epidermal appendages that contain both epithelial and mesenchymal compartments; the
dermal papilla (DP) is located at the base of hair follicle and is thought to be fundamental for hair follicle
morphogenesis and cycling
• DP cells treated with MSC-EVs displayed increased expression and secre2on of VEGF and IGF-1. Intradermal
injec2on of MSC-EVs into C57BL/6 mice promoted the conversion from telogen to anagen and increased
expression of wnt3a, wnt5a and versican was demonstrated. The ﬁrst 2me our results suggest that MSC-EVs
have a poten2al to ac2vate DP cells, prolonged survival, induce growth factor ac2va2on in vitro, and promotes
hair growth in vivo.