Table 3.

Cell therapy for the management of SCD

Cell therapies in SCD		In vivo Mechanism of Action	Cell Therapy Related - Benefits	Cell Therapy Related-Limitations
RBC exchange		↓HbS concentration and blood viscosity	Prevents or mitigates neurological disease and the associated comorbidities	Alloimmunization by repeated RBC transfusion
		↓the burden of sickled cells		Risk of iron overload
Allogeneic HSCT	HLA-matched sibling donor transplant	Restores normal hematopoiesis	Mitigates progressive organ dysfunction	Limitation of suitable donor
			97% Overall survival in	Conditioning regimens dependence
			10-15 year follow-up	Patient with end-organ damage usually excluded
			Lower rates of healthcare utilization	Transplantation related toxicity
	HLA-matched unrelated donor	Restores normal hematopoiesis	Mitigates progressive organ dysfunction	Lack of comprehensive donor registries
			Lower rates of healthcare utilization	Time for search process, coordination of donor
				High rates of graft rejection
				Conditioning regimen-dependence
				Outcomes related to age of donor and recipient
				Transplantation related toxicity
	Haploidentical donor	Myeloablative conditioning regimens required	Larger donor pool	High rates of graft rejection
			Available to most patients	Follow up less than 5 years
			Improvement in the intensity of the conditioning regimens
			↓Transplantation-related toxicity and graft failure
Autologous Hematopoietic Stem Cell gene-based therapy	Gene addition	CD34+ HSCs are genetically modified by adding a therapeutic β-globin gene with lentiviral transduction	Robust β-globin expression in erythroid cells	Toxicity of conditioning
				Risk of insertional oncogenesis and long-term high-level expression
				Reduces CD34+ HSCs engraftment ability
				Transplantation related - toxicity:
	Gene editing	CD34+ HSCs are genetically modified by CRISPR - based editing of a repressor protein	HbF induction	Minimal transplantation related - toxicity
			Avoiding insertional mutagenesis