Stem cell and its derivatives as drug delivery vehicles: an effective new strategy of drug delivery system

Figures & data

Table 1. Researches and developments of stem cell products.

Research phase	Manufacturer (Country)	Types of stem cells	Indication
Preclinical Stages.	Yan’an Hospital of Kunming City (China)	Human umbilical cord MSCs	Diabetic Nephropathy
	Celal Bayar University, Medical School (Turkey)	Autologous mesenchymal stem cell	Urticaria Autoimmune Diseases Immune System Diseases Skin Diseases
	Department of Orthopedics & Traumatology (Hong Kong)	Autologous MSCs	Osteoarthritis, Knee
	KyungHee University Gandong Hospital (Korea)	ASTROSTEM	Cerebral Palsy
	University of Florida Gainesville (America)	MESENCHYMAL STROMAL CELLS	Polymyositis Dermatomyositis
Clinical Trials	Graz University Hospital (Austria)	Hematopoietic stem cells from bone marrow or peripheral blood	Acute Myeloid Leukemia (AML)
	Mayo Clinic Rochester (America)	Autologous hematopoietic stem cell	Lymphoma
	University of Southern California University Hospital (America)	Adult human MSCs	Crohn’s Disease
	DBIM Hopital Saint Louis (France)	Autologous stem cell transplantation	Chronic Lymphocytic Leukemia
	Kanagawa Children’s Medical Center (Japan)	Autologous cardiac stem cells (JRM-001)	Hypoplastic Left Heart Syndrome Single Ventricle
In Clinics	Osiris (America)	Allogeneic BMSCs	GVHD and Crohn’s disease
	FCB-Pharmicell (Korea)	Autologous BMSCs	Polar myocardial infarction
	Corestem (Korea)	Autologous BMSCs	Muscle atrophy
	Vericel (America)	Autologous chondrocyte	Chondral injury
	Chiesi (Italy)	Autologous corneal stem cells	Moderate limbal stem cell deficiency
	Mesoblast (Australia)	Autologous Bone Marrow Mesenchymal Precursor Cell	Bone repair

Table 2. Characteristics of stem cell.

Characteristics	Drugs	Functions	References
Homing of tissue injury sites	PTX, VCR, TRAIL, NK4, Osteoprotegerin	Recruiting MSCs through chemokine and achieving targeted drug delivery	(Sadhukha et al. 2014; Hagenhoff et al. 2016; Timin et al. 2019)
Overexpression of transporters	PTX, VCR	Transporters actively efflux drugs from cells and exhibit drug resistance	(Sadhukha et al. 2014; Timin et al. 2019)
Immune compatibility	Stem cell	No allograft rejection and MSCs gradually cleared in vivo.	(Chiu 2005)
Low immunogenicity	Chondrogenically differentiated hBMSC	Escape the surveillance of the immune system	(Kiernan et al. 2018)
Anti-inflammatory or anti-tumor activity	MSCs, VCR	Combined with anti-inflammatory or anti-tumor drugs to enhance the efficacy	(Rhee et al. 2015; Zheng et al. 2015; Timin et al. 2019)

Figure 1. Homing/migration of MSCs towards target tissue/cells. Stem cells are injected into the blood vessel, and then participate in the surface adhesion factor-mediated stagnation on the vascular endothelial cells and rolling, adhesion and crawling. Subsequently, stem cells are induced to migrate across endothelial cells through receptor-ligand interaction. Later, chemoattractant-mediated migration in the interstitial of the target tissue and specific interaction with the target cell.

Figure 2. Stem cell and its derivatives as drug vehicle to deliver therapeutic drugs. Cell membranes, extracellular vesicles or exosomes, derived from stem cells, and stem cells themselves are all good drug delivery vehicles which loaded with therapeutic drugs in various ways, thereby delivering the drugs to the target site for the treatment of diseases.

Figure 3. Location of drugs in stem cell and its derivatives-based DDS. a, Surface adsorption caused by electrostatic force, van der Waals force and hydrogen bond. b, Endocytosis of stem cells. c, Chemical bond modification. d, Antigen antibody reaction. e, Biotin reacts with avidin. f, Effects of cell penetrating peptide.

Figure 4. Stem cell as drug vehicle deliver anticancer agents to treat cancer. Stem cells as a vehicle to contain drugs for the treatment of cancer, including small molecule chemotherapeutics, antibody drugs, nucleic acid drugs, polypeptide or protein drugs and oncolytic virus drugs. The drug-loaded stem cells get into the cancer tissue through the blood and release anti-cancer agents. Thereby exerting a therapeutic effect.

Figure 5. Stem cells deliver cargos for tissue repair and regenerative medicine. Stem cell are used in regenerative medicine through transplantation due to their strong self-renewal and multilineage differentiation characteristics, including bone regeneration, cartilage regeneration, myocardial regeneration, nerve regeneration and so on. In addition, stem cell promotes vascular regeneration through powerful paracrine effects, enhance immune regulation and reduce inflammation, promote extracellular matrix and tissue remodeling, thereby promoting tissue damage repair. Stem cell promotes the overexpression of genes such as TGF-β3 and IGF-1 through genetic engineering, and promote tissue repair.

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Data availability statement

Data sharing is not applicable to this article as no new data created or analyzed in this study.